Matrix Metalloproteinase Inhibitors as Investigative Tools in the Pathogenesis and Management of Vascular Disease

  • Mina M. Benjamin
  • Raouf A. Khalil
Part of the Experientia Supplementum book series (EXS, volume 103)


Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM). MMPs could also regulate the activity of several non-ECM bioactive substrates and consequently affect different cellular functions. Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and others. Pro-MMPs are cleaved into active MMPs, which in turn act on various substrates in the ECM and on the cell surface. MMPs play an important role in the regulation of numerous physiological processes including vascular remodeling and angiogenesis. MMPs may also be involved in vascular diseases such as hypertension, atherosclerosis, aortic aneurysm, and varicose veins. MMPs also play a role in the hemodynamic and vascular changes associated with pregnancy and preeclampsia. The role of MMPs is commonly assessed by measuring their gene expression, protein amount, and proteolytic activity using gel zymography. Because there are no specific activators of MMPs, MMP inhibitors are often used to investigate the role of MMPs in different physiologic processes and in the pathogenesis of specific diseases. MMP inhibitors include endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as zinc chelators, doxycycline, and marimastat. MMP inhibitors have been evaluated as diagnostic and therapeutic tools in cancer, autoimmune disease, and cardiovascular disease. Although several MMP inhibitors have been synthesized and tested both experimentally and clinically, only one MMP inhibitor, i.e., doxycycline, is currently approved by the Food and Drug Administration. This is mainly due to the undesirable side effects of MMP inhibitors especially on the musculoskeletal system. While most experimental and clinical trials of MMP inhibitors have not demonstrated significant benefits, some trials still showed promising results. With the advent of new genetic and pharmacological tools, disease-specific MMP inhibitors with fewer undesirable effects are being developed and could be useful in the management of vascular disease.


Aneurysm Angiogenesis Atherosclerosis Endothelium Extracellular matrix Hypertension Preeclampsia Pregnancy TIMP Varicose veins Vascular smooth muscle 



Abdominal aortic aneurysm


A disintegrin and metalloproteinase


Blood pressure


Endothelial cell


Extracellular matrix


Fibroblast growth factor


G-protein-coupled receptor


Human umbilical vein endothelial cells


Insulin-like growth factor


Mitogen-activated protein kinase


Matrix metalloproteinase


Myocardial infarction


Nitric oxide




Protein kinase C


Transforming growth factor


Tissue inhibitor of matrix metalloproteinase


Tumor necrosis factor


Vascular endothelial growth factor


Vascular smooth muscle



This work was supported by grants from National Heart, Lung, and Blood Institute (HL-65998, HL-98724) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-60702).


  1. Agrawal A, Romero-Perez D, Jacobsen JA, Villarreal FJ, Cohen SM (2008) Zinc-binding groups modulate selective inhibition of MMPs. ChemMedChem 3:812–820CrossRefPubMedGoogle Scholar
  2. Aguilera CM, George SJ, Johnson JL, Newby AC (2003) Relationship between type IV collagen degradation, metalloproteinase activity and smooth muscle cell migration and proliferation in cultured human saphenous vein. Cardiovasc Res 58:679–688CrossRefPubMedGoogle Scholar
  3. Ahokas K, Lohi J, Illman SA, Llano E, Elomaa O, Impola U, Karjalainen-Lindsberg ML, Saarialho-Kere U (2003) Matrix metalloproteinase-21 is expressed epithelially during development and in cancer and is up-regulated by transforming growth factor-beta1 in keratinocytes. Lab Invest 83:1887–1899CrossRefPubMedGoogle Scholar
  4. Aikawa M, Rabkin E, Voglic SJ, Shing H, Nagai R, Schoen FJ, Libby P (1998) Lipid lowering promotes accumulation of mature smooth muscle cells expressing smooth muscle myosin heavy chain isoforms in rabbit atheroma. Circ Res 83:1015–1026PubMedGoogle Scholar
  5. Aimes RT, Quigley JP (1995) Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J Biol Chem 270:5872–5876CrossRefPubMedGoogle Scholar
  6. Akiba S, Kumazawa S, Yamaguchi H, Hontani N, Matsumoto T, Ikeda T, Oka M, Sato T (2006) Acceleration of matrix metalloproteinase-1 production and activation of platelet-derived growth factor receptor beta in human coronary smooth muscle cells by oxidized LDL and 4-hydroxynonenal. Biochim Biophys Acta 1763:797–804CrossRefPubMedGoogle Scholar
  7. Alfranca A, Lopez-Oliva JM, Genis L, Lopez-Maderuelo D, Mirones I, Salvado D, Quesada AJ, Arroyo AG, Redondo JM (2008) PGE2 induces angiogenesis via MT1-MMP-mediated activation of the TGFbeta/Alk5 signaling pathway. Blood 112:1120–1128CrossRefPubMedGoogle Scholar
  8. Almeida EA, Ilic D, Han Q, Hauck CR, Jin F, Kawakatsu H, Schlaepfer DD, Damsky CH (2000) Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase. J Cell Biol 149:741–754CrossRefPubMedGoogle Scholar
  9. Amour A, Knight CG, Webster A, Slocombe PM, Stephens PE, Knäuper V, Docherty AJ, Murphy G (2000) The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. FEBS Lett 473:275–279CrossRefPubMedGoogle Scholar
  10. Annes JP, Munger JS, Rifkin DB (2003) Making sense of latent TGFbeta activation. J Cell Sci 116:217–224CrossRefPubMedGoogle Scholar
  11. Aravind B, Saunders B, Navin T, Sandison A, Monaco C (2010) Paleolog EM and Davies AH Inhibitory effect of TIMP influences the morphology of varicose veins. Eur J Vasc Endovasc Surg 40:754–765CrossRefPubMedGoogle Scholar
  12. Ardi VC, Van den Steen PE, Opdenakker G, Schweighofer B, Deryugina EI, Quigley JP (2009) Neutrophil MMP-9 proenzyme, unencumbered by TIMP-1, undergoes efficient activation in vivo and catalytically induces angiogenesis via a basic fibroblast growth factor (FGF-2)/FGFR-2 pathway. J Biol Chem 284:25854–25866CrossRefPubMedGoogle Scholar
  13. Armani C, Curcio M, Barsotti MC, Santoni T, Di Stefano R, Dell’omodarme M, Brandi ML, Ferrari M, Scatena F, Carpi A, Balbarini A (2007) Polymorphic analysis of the matrix metalloproteinase-9 gene and susceptibility to sporadic abdominal aortic aneurysm. Biomed Pharmacother 61:268–271CrossRefPubMedGoogle Scholar
  14. Asamoto M, Hokaiwado N, Cho YM, Takahashi S, Ikeda Y, Imaida K, Shirai T (2001) Prostate carcinomas developing in transgenic rats with SV40 T antigen expression under probasin promoter control are strictly androgen dependent. Cancer Res 61:4693–4700PubMedGoogle Scholar
  15. Auge F, Hornebeck W, Decarme M, Laronze JY (2003) Improved gelatinase a selectivity by novel zinc binding groups containing galardin derivatives. Bioorg Med Chem Lett 13:1783–1786CrossRefPubMedGoogle Scholar
  16. Axisa B, Loftus IM, Naylor AR, Goodall S, Jones L, Bell PR, Thompson MM (2002) Prospective, randomized, double-blind trial investigating the effect of doxycycline on matrix metalloproteinase expression within atherosclerotic carotid plaques. Stroke 33:2858–2864CrossRefPubMedGoogle Scholar
  17. Badier-Commander C, Verbeuren T, Lebard C, Michel JB, Jacob MP (2000) Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation. J Pathol 192:105–112CrossRefPubMedGoogle Scholar
  18. Baker AH, Zaltsman AB, George SJ, Newby AC (1998) Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. TIMP-3 promotes apoptosis. J Clin Invest 101:1478–1487CrossRefPubMedGoogle Scholar
  19. Baker AH, Edwards DR, Murphy G (2002) Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci 115:3719–3727CrossRefPubMedGoogle Scholar
  20. Banke IJ, Arlt MJ, Mueller MM, Sperl S, Stemberger A, Sturzebecher J, Amirkhosravi A, Moroder L, Kruger A (2005) Effective inhibition of experimental metastasis and prolongation of survival in mice by a potent factor Xa-specific synthetic serine protease inhibitor with weak anticoagulant activity. Thromb Haemost 94:1084–1093PubMedGoogle Scholar
  21. Barbour JR, Stroud RE, Lowry AS, Clark LL, Leone AM, Jones JA, Spinale FG, Ikonomidis JS (2006) Temporal disparity in the induction of matrix metalloproteinases and tissue inhibitors of metalloproteinases after thoracic aortic aneurysm formation. J Thorac Cardiovasc Surg 132:788–795CrossRefPubMedGoogle Scholar
  22. Barbour JR, Spinale FG, Ikonomidis JS (2007) Proteinase systems and thoracic aortic aneurysm progression. J Surg Res 139:292–307CrossRefPubMedGoogle Scholar
  23. Bar-Or A, Nuttall RK, Duddy M, Alter A, Kim HJ, Ifergan I, Pennington CJ, Bourgoin P, Edwards DR, Yong VW (2003) Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis. Brain 126:2738–2749CrossRefPubMedGoogle Scholar
  24. Barron LA, Giardina JB, Granger JP, Khalil RA (2001) High-salt diet enhances vascular reactivity in pregnant rats with normal and reduced uterine perfusion pressure. Hypertension 38:730–735PubMedGoogle Scholar
  25. Basile JR, Holmbeck K, Bugge TH, Gutkind JS (2007) MT1-MMP controls tumor-induced angiogenesis through the release of semaphorin 4D. J Biol Chem 282:6899–6905CrossRefPubMedGoogle Scholar
  26. Beaudeux JL, Giral P, Bruckert E, Foglietti MJ, Chapman MJ (2004) Matrix metalloproteinases, inflammation and atherosclerosis: therapeutic perspectives. Clin Chem Lab Med 42:121–131PubMedGoogle Scholar
  27. Bendeck MP, Irvin C, Reidy MA (1996) Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury. Circ Res 78:38–43PubMedGoogle Scholar
  28. Bendeck MP, Conte M, Zhang M, Nili N, Strauss BH, Farwell SM (2002) Doxycycline modulates smooth muscle cell growth, migration, and matrix remodeling after arterial injury. Am J Pathol 160:1089–1095CrossRefPubMedGoogle Scholar
  29. Bendrik C, Karlsson L, Dabrosin C (2010) Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer. Cancer Lett 292:32–40CrossRefPubMedGoogle Scholar
  30. Bergan JJ, Schmid-Schonbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B (2006) Chronic venous disease. N Engl J Med 355:488–498CrossRefPubMedGoogle Scholar
  31. Bernardo MM, Brown S, Li ZH, Fridman R, Mobashery S (2002) Design, synthesis, and characterization of potent, slow-binding inhibitors that are selective for gelatinases. J Biol Chem 277:11201–11207CrossRefPubMedGoogle Scholar
  32. Biasone A, Tortorella P, Campestre C, Agamennone M, Preziuso S, Chiappini M, Nuti E, Carelli P, Rossello A, Mazza F, Gallina C (2007) alpha-Biphenylsulfonylamino 2-methylpropyl phosphonates: enantioselective synthesis and selective inhibition of MMPs. Bioorg Med Chem 15:791–799CrossRefPubMedGoogle Scholar
  33. Blagg JA, Noe MC, Wolf-Gouveia LA, Reiter LA, Laird ER, Chang SP, Danley DE, Downs JT, Elliott NC, Eskra JD, Griffiths RJ, Hardink JR, Haugeto AI, Jones CS, Liras JL, Lopresti-Morrow LL, Mitchell PG, Pandit J, Robinson RP, Subramanyam C, Vaughn-Bowser ML, Yocum SA (2005) Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14. Bioorg Med Chem Lett 15:1807–1810CrossRefPubMedGoogle Scholar
  34. Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G, Meyer J, Cambien F, Tiret L (2003) Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 107:1579–1585CrossRefPubMedGoogle Scholar
  35. Bode W, Gomis-Ruth FX, Stockler W (1993) Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the ‘metzincins’. FEBS Lett 331:134–140CrossRefPubMedGoogle Scholar
  36. Boire A, Covic L, Agarwal A, Jacques S, Sherifi S, Kuliopulos A (2005) PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 120:303–313CrossRefPubMedGoogle Scholar
  37. Bond M, Murphy G, Bennett MR, Amour A, Knauper V, Newby AC, Baker AH (2000) Localization of the death domain of tissue inhibitor of metalloproteinase-3 to the N terminus. Metalloproteinase inhibition is associated with proapoptotic activity. J Biol Chem 275:41358–41363CrossRefPubMedGoogle Scholar
  38. Bonfil RD, Sabbota A, Nabha S, Bernardo MM, Dong Z, Meng H, Yamamoto H, Chinni SR, Lim IT, Chang M, Filetti LC, Mobashery S, Cher ML, Fridman R (2006) Inhibition of human prostate cancer growth, osteolysis and angiogenesis in a bone metastasis model by a novel mechanism-based selective gelatinase inhibitor. Int J Cancer 118:2721–2726CrossRefPubMedGoogle Scholar
  39. Bonfil RD, Dong Z, Trindade Filho JC, Sabbota A, Osenkowski P, Nabha S, Yamamoto H, Chinni SR, Zhao H, Mobashery S, Vessella RL, Fridman R, Cher ML (2007) Prostate cancer-associated membrane type 1-matrix metalloproteinase: a pivotal role in bone response and intraosseous tumor growth. Am J Pathol 170:2100–2111CrossRefPubMedGoogle Scholar
  40. Borkakoti N, Winkler FK, Williams DH, D’Arcy A, Broadhurst MJ, Brown PA, Johnson WH, Murray EJ (1994) Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor. Nat Struct Biol 1:106–110CrossRefPubMedGoogle Scholar
  41. Bosman FT, Stamenkovic I (2003) Functional structure and composition of the extracellular matrix. J Pathol 200:423–428CrossRefPubMedGoogle Scholar
  42. Bremer C, Tung CH, Weissleder R (2001) In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med 7:743–748CrossRefPubMedGoogle Scholar
  43. Breuer E, Salomon CJ, Katz Y, Chen W, Lu S, Roschenthaler GV, Hadar R, Reich R (2004) Carbamoylphosphonates, a new class of in vivo active matrix metalloproteinase inhibitors. 1. Alkyl- and cycloalkylcarbamoylphosphonic acids. J Med Chem 47:2826–2832CrossRefPubMedGoogle Scholar
  44. Brown S, Meroueh SO, Fridman R, Mobashery S (2004) Quest for selectivity in inhibition of matrix metalloproteinases. Curr Top Med Chem 4:1227–1238CrossRefPubMedGoogle Scholar
  45. Browner MF, Smith WW, Castelhano AL (1995) Matrilysin-inhibitor complexes: common themes among metalloproteases. Biochemistry 34:6602–6610CrossRefPubMedGoogle Scholar
  46. Brunner S, Kim JO, Methe H (2010) Relation of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio in peripheral circulating CD14+ monocytes to progression of coronary artery disease. Am J Cardiol 105:429–434CrossRefPubMedGoogle Scholar
  47. Butler GS, Butler MJ, Atkinson SJ, Will H, Tamura T, Schade van Westrum S, Crabbe T, Clements J, d’Ortho MP, Murphy G (1998) The TIMP2 membrane type 1 metalloproteinase “receptor” regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem 273:871–880CrossRefPubMedGoogle Scholar
  48. Campestre C, Agamennone M, Tortorella P, Preziuso S, Biasone A, Gavuzzo E, Pochetti G, Mazza F, Hiller O, Tschesche H, Consalvi V, Gallina C (2006) N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: mode of binding in a complex with MMP-8. Bioorg Med Chem Lett 16:20–24CrossRefPubMedGoogle Scholar
  49. Carragher NO, Frame MC (2004) Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion. Trends Cell Biol 14:241–249CrossRefPubMedGoogle Scholar
  50. Castro MM, Rizzi E, Rodrigues GJ, Ceron CS, Bendhack LM, Gerlach RF, Tanus-Santos JE (2009) Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension. Free Radic Biol Med 46:1298–1307CrossRefPubMedGoogle Scholar
  51. Castro MM, Rizzi E, Prado CM, Rossi MA, Tanus-Santos JE, Gerlach RF (2010) Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling. Matrix Biol 29:194–201CrossRefPubMedGoogle Scholar
  52. Cauwe B, Van den Steen PE, Opdenakker G (2007) The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 42:113–185CrossRefPubMedGoogle Scholar
  53. Celenza G, Villegas-Estrada A, Lee M, Boggess B, Forbes C, Wolter WR, Suckow MA, Mobashery S, Chang M (2008) Metabolism of (4-phenoxyphenylsulfonyl) methylthiirane, a selective gelatinase inhibitor. Chem Biol Drug Des 71:187–196CrossRefPubMedGoogle Scholar
  54. Cena J, Lalu MM, Rosenfelt C, Schulz R (2008) Endothelial dependence of matrix metalloproteinase-mediated vascular hyporeactivity caused by lipopolysaccharide. Eur J Pharmacol 582:116–122CrossRefPubMedGoogle Scholar
  55. Cevik C, Otahbachi M, Nugent K, Warangkana C, Meyerrose G (2008) Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition on serum matrix metalloproteinase-13 and tissue inhibitor matrix metalloproteinase-1 levels as a sign of plaque stabilization. J Cardiovasc Med (Hagerstown) 9:1274–1278CrossRefGoogle Scholar
  56. Chen LC, Noelken ME, Nagase H (1993) Disruption of the cysteine-75 and zinc ion coordination is not sufficient to activate the precursor of human matrix metalloproteinase 3 (stromelysin 1). Biochemistry 32:10289–10295CrossRefPubMedGoogle Scholar
  57. Chen J, Tung CH, Mahmood U, Ntziachristos V, Gyurko R, Fishman MC, Huang PL, Weissleder R (2002) In vivo imaging of proteolytic activity in atherosclerosis. Circulation 105:2766–2771CrossRefPubMedGoogle Scholar
  58. Chen L, Wang X, Carter SA, Shen YH, Bartsch HR, Thompson RW, Coselli JS, Wilcken DL, Wang XL, LeMaire SA (2006) A single nucleotide polymorphism in the matrix metalloproteinase 9 gene (-8202A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection. J Thorac Cardiovasc Surg 131:1045–1052CrossRefPubMedGoogle Scholar
  59. Cheng XW, Kuzuya M, Sasaki T, Arakawa K, Kanda S, Sumi D, Koike T, Maeda K, Tamaya-Mori N, Shi GP, Saito N, Iguchi A (2004) Increased expression of elastolytic cysteine proteases, cathepsins S and K, in the neointima of balloon-injured rat carotid arteries. Am J Pathol 164:243–251CrossRefPubMedGoogle Scholar
  60. Cherney RJ, Mo R, Meyer DT, Hardman KD, Liu RQ, Covington MB, Qian M, Wasserman ZR, Christ DD, Trzaskos JM, Newton RC, Decicco CP (2004) Sultam hydroxamates as novel matrix metalloproteinase inhibitors. J Med Chem 47:2981–2983CrossRefPubMedGoogle Scholar
  61. Chew DK, Conte MS, Khalil RA (2004) Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular contraction. J Vasc Surg 40:1001–1010CrossRefPubMedGoogle Scholar
  62. Cho A, Reidy MA (2002) Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res 91:845–851CrossRefPubMedGoogle Scholar
  63. Choi ET, Collins ET, Marine LA, Uberti MG, Uchida H, Leidenfrost JE, Khan MF, Boc KP, Abendschein DR, Parks WC (2005) Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 25:1020–1025CrossRefPubMedGoogle Scholar
  64. Choke E, Cockerill GW, Dawson J, Wilson RW, Jones A, Loftus IM, Thompson MM (2006) Increased angiogenesis at the site of abdominal aortic aneurysm rupture. Ann N Y Acad Sci 1085:315–319CrossRefPubMedGoogle Scholar
  65. Chung AS, Kao WJ (2009) Fibroblasts regulate monocyte response to ECM-derived matrix: the effects on monocyte adhesion and the production of inflammatory, matrix remodeling, and growth factor proteins. J Biomed Mater Res A 89:841–853PubMedGoogle Scholar
  66. Chung L, Dinakarpandian D, Yoshida N, Lauer-Fields JL, Fields GB, Visse R, Nagase H (2004) Collagenase unwinds triple-helical collagen prior to peptide bond hydrolysis. EMBO J 23:3020–3030CrossRefPubMedGoogle Scholar
  67. Chung AW, Yang HH, Radomski MW, van Breemen C (2008) Long-term doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in Marfan syndrome through the inhibition of matrix metalloproteinase-2 and -9. Circ Res 102:e73–e85CrossRefPubMedGoogle Scholar
  68. Churg A, Wang RD, Tai H, Wang X, Xie C, Dai J, Shapiro SD, Wright JL (2003) Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-alpha release. Am J Respir Crit Care Med 167:1083–1089CrossRefPubMedGoogle Scholar
  69. Cohen M, Wuillemin C, Irion O, Bischof P (2010) Role of decidua in trophoblastic invasion. Neuro Endocrinol Lett 31:193–197PubMedGoogle Scholar
  70. Cook GR, Manivannan E, Underdahl T, Lukacova V, Zhang Y, Balaz S (2004) Synthesis and evaluation of novel oxazoline MMP inhibitors. Bioorg Med Chem Lett 14:4935–4939CrossRefPubMedGoogle Scholar
  71. Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295:2387–2392CrossRefPubMedGoogle Scholar
  72. Creemers EE, Davis JN, Parkhurst AM, Leenders P, Dowdy KB, Hapke E, Hauet AM, Escobar PG, Cleutjens JP, Smits JF, Daemen MJ, Zile MR, Spinale FG (2003) Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice. Am J Physiol Heart Circ Physiol 284:H364–H371PubMedGoogle Scholar
  73. Cui Y, Takamatsu H, Kakiuchi T, Ohba H, Kataoka Y, Yokoyama C, Onoe H, Watanabe Y, Hosoya T, Suzuki M, Noyori R, Tsukada H (2006) Neuroprotection by a central nervous system-type prostacyclin receptor ligand demonstrated in monkeys subjected to middle cerebral artery occlusion and reperfusion: a positron emission tomography study. Stroke 37:2830–2836CrossRefPubMedGoogle Scholar
  74. Dalvie D, Cosker T, Boyden T, Zhou S, Schroeder C, Potchoiba MJ (2008) Metabolism distribution and excretion of a matrix metalloproteinase-13 inhibitor, 4-[4-(4-fluorophenoxy)-benzenesulfonylamino]tetrahydropyran-4-carboxylic acid hydroxyamide (CP-544439), in rats and dogs: assessment of the metabolic profile of CP-544439 in plasma and urine of humans. Drug Metab Dispos 36:1869–1883CrossRefPubMedGoogle Scholar
  75. Davies B, Brown PD, East N, Crimmin MJ, Balkwill FR (1993) A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts. Cancer Res 53(9):2087–2091PubMedGoogle Scholar
  76. de Jager CA, Linton EA, Spyropoulou I, Sargent IL, Redman CW (2003) Matrix metalloprotease-9, placental syncytiotrophoblast and the endothelial dysfunction of pre-eclampsia. Placenta 24:84–91CrossRefPubMedGoogle Scholar
  77. Derosa G, D’Angelo A, Ciccarelli L, Piccinni MN, Pricolo F, Salvadeo S, Montagna L, Gravina A, Ferrari I, Galli S, Paniga S, Tinelli C, Cicero AF (2006) Matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinase-1 in patients with hypertension. Endothelium 13:227–231CrossRefPubMedGoogle Scholar
  78. Desrochers PE, Mookhtiar K, Van Wart HE, Hasty KA, Weiss SJ (1992) Proteolytic inactivation of alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin by oxidatively activated human neutrophil metalloproteinases. J Biol Chem 267:5005–5012PubMedGoogle Scholar
  79. Dhingra R, Pencina MJ, Schrader P, Wang TJ, Levy D, Pencina K, Siwik DA, Colucci WS, Benjamin EJ, Vasan RS (2009) Relations of matrix remodeling biomarkers to blood pressure progression and incidence of hypertension in the community. Circulation 119:1101–1107CrossRefPubMedGoogle Scholar
  80. Djuric T, Zivkovic M, Stankovic A, Kolakovic A, Jekic D, Selakovic V, Alavantic D (2010) Plasma levels of matrix metalloproteinase-8 in patients with carotid atherosclerosis. J Clin Lab Anal 24:246–251CrossRefPubMedGoogle Scholar
  81. Dollery CM, Libby P (2006) Atherosclerosis and proteinase activation. Cardiovasc Res 69:625–635CrossRefPubMedGoogle Scholar
  82. Du WD, Zhang YE, Zhai WR, Zhou XM (1999) Dynamic changes of type I, III and IV collagen synthesis and distribution of collagen-producing cells in carbon tetrachloride-induced rat liver fibrosis. World J Gastroenterol 5:397–403PubMedGoogle Scholar
  83. Dublanchet AC, Ducrot P, Andrianjara C, O’Gara M, Morales R, Compere D, Denis A, Blais S, Cluzeau P, Courte K, Hamon J, Moreau F, Prunet ML, Tertre A (2005) Structure-based design and synthesis of novel non-zinc chelating MMP-12 inhibitors. Bioorg Med Chem Lett 15:3787–3790CrossRefPubMedGoogle Scholar
  84. Ducharme A, Frantz S, Aikawa M, Rabkin E, Lindsey M, Rohde LE, Schoen FJ, Kelly RA, Werb Z, Libby P, Lee RT (2000) Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest 106:55–62CrossRefPubMedGoogle Scholar
  85. Eck SM, Blackburn JS, Schmucker AC, Burrage PS, Brinckerhoff CE (2009) Matrix metalloproteinase and G protein coupled receptors: co-conspirators in the pathogenesis of autoimmune disease and cancer. J Autoimmun 33:214–221CrossRefPubMedGoogle Scholar
  86. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174CrossRefPubMedGoogle Scholar
  87. Elaut G, Rogiers V, Vanhaecke T (2007) The pharmaceutical potential of histone deacetylase inhibitors. Curr Pharm Des 13:2584–2620CrossRefPubMedGoogle Scholar
  88. El-Bradey MH, Cheng L, Bartsch DU, Niessman M, El-Musharaf A, Freeman WR (2004) The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinase, on a new animal model of epiretinal membrane. Retina 24:783–789CrossRefPubMedGoogle Scholar
  89. Engel CK, Pirard B, Schimanski S, Kirsch R, Habermann J, Klingler O, Schlotte V, Weithmann KU, Wendt KU (2005) Structural basis for the highly selective inhibition of MMP-13. Chem Biol 12:181–189CrossRefPubMedGoogle Scholar
  90. English WR, Holtz B, Vogt G, Knauper V, Murphy G (2001) Characterization of the role of the “MT-loop”: an eight-amino acid insertion specific to progelatinase A (MMP2) activating membrane-type matrix metalloproteinases. J Biol Chem 276:42018–42026CrossRefPubMedGoogle Scholar
  91. Erdozain OJ, Pegrum S, Winrow VR, Horrocks M, Stevens CR (2011) Hypoxia in abdominal aortic aneurysm supports a role for HIF-1alpha and Ets-1 as drivers of matrix metalloproteinase upregulation in human aortic smooth muscle cells. J Vasc Res 48:163–170CrossRefPubMedGoogle Scholar
  92. Eugster T, Huber A, Obeid T, Schwegler I, Gurke L, Stierli P (2005) Aminoterminal propeptide of type III procollagen and matrix metalloproteinases-2 and -9 failed to serve as serum markers for abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 29:378–382PubMedGoogle Scholar
  93. Ezhilarasan R, Jadhav U, Mohanam I, Rao JS, Gujrati M, Mohanam S (2009) The hemopexin domain of MMP-9 inhibits angiogenesis and retards the growth of intracranial glioblastoma xenograft in nude mice. Int J Cancer 124:306–315CrossRefPubMedGoogle Scholar
  94. Fata JE, Leco KJ, Voura EB, Yu HY, Waterhouse P, Murphy G, Moorehead RA, Khokha R (2001) Accelerated apoptosis in the Timp-3-deficient mammary gland. J Clin Invest 108:831–841PubMedGoogle Scholar
  95. Fedak PW, Smookler DS, Kassiri Z, Ohno N, Leco KJ, Verma S, Mickle DA, Watson KL, Hojilla CV, Cruz W, Weisel RD, Li RK, Khokha R (2004) TIMP-3 deficiency leads to dilated cardiomyopathy. Circulation 110:2401–2409CrossRefPubMedGoogle Scholar
  96. Feng X, Tonnesen MG, Peerschke EI, Ghebrehiwet B (2002) Cooperation of C1q receptors and integrins in C1q-mediated endothelial cell adhesion and spreading. J Immunol 168:2441–2448PubMedGoogle Scholar
  97. Fingleton B (2008) MMPs as therapeutic targets – still a viable option? Semin Cell Dev Biol 19:61–68CrossRefPubMedGoogle Scholar
  98. Fitzsimmons PJ, Forough R, Lawrence ME, Gantt DS, Rajab MH, Kim H, Weylie B, Spiekerman AM, Dehmer GJ (2007) Urinary levels of matrix metalloproteinase 9 and 2 and tissue inhibitor of matrix metalloproteinase in patients with coronary artery disease. Atherosclerosis 194:196–203CrossRefPubMedGoogle Scholar
  99. Flamant M, Placier S, Dubroca C, Esposito B, Lopes I, Chatziantoniou C, Tedgui A, Dussaule JC, Lehoux S (2007) Role of matrix metalloproteinases in early hypertensive vascular remodeling. Hypertension 50:212–218CrossRefPubMedGoogle Scholar
  100. Foda HD, Rollo EE, Drews M, Conner C, Appelt K, Shalinsky DR, Zucker S (2001) Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN: attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340). Am J Respir Cell Mol Biol 25:717–724PubMedGoogle Scholar
  101. Foley LH, Palermo R, Dunten P, Wang P (2001) Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. Bioorg Med Chem Lett 11:969–972CrossRefPubMedGoogle Scholar
  102. Folgueras AR, Fueyo A, Garcia-Suarez O, Cox J, Astudillo A, Tortorella P, Campestre C, Gutierrez-Fernandez A, Fanjul-Fernandez M, Pennington CJ, Edwards DR, Overall CM, Lopez-Otin C (2008) Collagenase-2 deficiency or inhibition impairs experimental autoimmune encephalomyelitis in mice. J Biol Chem 283:9465–9474CrossRefPubMedGoogle Scholar
  103. Folkman J (2006) Antiangiogenesis in cancer therapy – endostatin and its mechanisms of action. Exp Cell Res 312:594–607CrossRefPubMedGoogle Scholar
  104. Forough R, Koyama N, Hasenstab D, Lea H, Clowes M, Nikkari ST, Clowes AW (1996) Overexpression of tissue inhibitor of matrix metalloproteinase-1 inhibits vascular smooth muscle cell functions in vitro and in vivo. Circ Res 79:812–820PubMedGoogle Scholar
  105. Franz M, Berndt A, Altendorf-Hofmann A, Fiedler N, Richter P, Schumm J, Fritzenwanger M, Figulla HR, Brehm BR (2009) Serum levels of large tenascin-C variants, matrix metalloproteinase-9, and tissue inhibitors of matrix metalloproteinases in concentric versus eccentric left ventricular hypertrophy. Eur J Heart Fail 11:1057–1062CrossRefPubMedGoogle Scholar
  106. Freeman-Cook KD, Reiter LA, Noe MC, Antipas AS, Danley DE, Datta K, Downs JT, Eisenbeis S, Eskra JD, Garmene DJ, Greer EM, Griffiths RJ, Guzman R, Hardink JR, Janat F, Jones CS, Martinelli GJ, Mitchell PG, Laird ER, Liras JL, Lopresti-Morrow LL, Pandit J, Reilly UD, Robertson D, Vaughn-Bowser ML, Wolf-Gouviea LA, Yocum SA (2007) Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg Med Chem Lett 17:6529–6534CrossRefPubMedGoogle Scholar
  107. Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13:555–562CrossRefPubMedGoogle Scholar
  108. Fu X, Kassim SY, Parks WC, Heinecke JW (2001) Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem 276:41279–41287CrossRefPubMedGoogle Scholar
  109. Fu X, Kao JL, Bergt C, Kassim SY, Huq NP, d’Avignon A, Parks WC, Mecham RP, Heinecke JW (2004) Oxidative cross-linking of tryptophan to glycine restrains matrix metalloproteinase activity: specific structural motifs control protein oxidation. J Biol Chem 279:6209–6212CrossRefPubMedGoogle Scholar
  110. Fujiwara K, Matsukawa A, Ohkawara S, Takagi K, Yoshinaga M (2002) Functional distinction between CXC chemokines, interleukin-8 (IL-8), and growth related oncogene (GRO)alpha in neutrophil infiltration. Lab Invest 82:15–23CrossRefPubMedGoogle Scholar
  111. Fukumoto Y, Deguchi JO, Libby P, Rabkin-Aikawa E, Sakata Y, Chin MT, Hill CC, Lawler PR, Varo N, Schoen FJ, Krane SM, Aikawa M (2004) Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques. Circulation 110:1953–1959CrossRefPubMedGoogle Scholar
  112. Galewska Z, Bankowski E, Romanowicz L, Jaworski S (2003) Pre-eclampsia (EPH-gestosis)-induced decrease of MMP-s content in the umbilical cord artery. Clin Chim Acta 335:109–115CrossRefPubMedGoogle Scholar
  113. Galewska Z, Romanowicz L, Gogiel T, Jaworski S, Bankowski E (2006) The inhibitory effect of preeclamptic umbilical cord blood serum on matrix metalloproteinase-1 in arterial slices incubated in vitro. Pathobiology 73:310–316CrossRefPubMedGoogle Scholar
  114. Galewska Z, Romanowicz L, Jaworski S, Bankowski E (2008) Gelatinase matrix metalloproteinase (MMP)-2 and MMP-9 of the umbilical cord blood in preeclampsia. Clin Chem Lab Med 46:517–522CrossRefPubMedGoogle Scholar
  115. Galewska Z, Romanowicz L, Jaworski S, Bankowski E (2010) Matrix metalloproteinases, MMP-7 and MMP-26, in plasma and serum of control and preeclamptic umbilical cord blood. Eur J Obstet Gynecol Reprod Biol 150:152–156CrossRefPubMedGoogle Scholar
  116. Galis ZS, Sukhova GK, Lark MW, Libby P (1994) Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 94:2493–2503CrossRefPubMedGoogle Scholar
  117. Galis ZS, Johnson C, Godin D, Magid R, Shipley JM, Senior RM, Ivan E (2002) Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res 91:852–859CrossRefPubMedGoogle Scholar
  118. Gallery ED, Campbell S, Arkell J, Nguyen M, Jackson CJ (1999) Preeclamptic decidual microvascular endothelial cells express lower levels of matrix metalloproteinase-1 than normals. Microvasc Res 57:340–346CrossRefPubMedGoogle Scholar
  119. Gandhi RH, Irizarry E, Nackman GB, Halpern VJ, Mulcare RJ, Tilson MD (1993) Analysis of the connective tissue matrix and proteolytic activity of primary varicose veins. J Vasc Surg 18:814–820CrossRefPubMedGoogle Scholar
  120. Ganz T (1999) Defensins and host defense. Science 286:420–421CrossRefPubMedGoogle Scholar
  121. Garcia C, Bartsch DU, Rivero ME, Hagedorn M, McDermott CD, Bergeron-Lynn G, Cheng L, Appelt K, Freeman WR (2002) Efficacy of Prinomastat (AG3340), a matrix metalloprotease inhibitor, in treatment of retinal neovascularization. Curr Eye Res 24:33–38CrossRefPubMedGoogle Scholar
  122. Gaubatz JW, Ballantyne CM, Wasserman BA, He M, Chambless LE, Boerwinkle E, Hoogeveen RC (2010) Association of circulating matrix metalloproteinases with carotid artery characteristics: The Atherosclerosis Risk in Communities Carotid MRI Study. Arterioscler Thromb Vasc Biol 30:1034–1042CrossRefPubMedGoogle Scholar
  123. Gearing AJ, Thorpe SJ, Miller K, Mangan M, Varley PG, Dudgeon T, Ward G, Turner C, Thorpe R (2002) Selective cleavage of human IgG by the matrix metalloproteinases, matrilysin and stromelysin. Immunol Lett 81:41–48CrossRefPubMedGoogle Scholar
  124. Geng YJ, Libby P (2002) Progression of atheroma: a struggle between death and procreation. Arterioscler Thromb Vasc Biol 22:1370–1380CrossRefPubMedGoogle Scholar
  125. Geng L, Wang W, Chen Y, Cao J, Lu L, Chen Q, He R, Shen W (2010) Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model. Exp Mol Pathol 89:72–81CrossRefPubMedGoogle Scholar
  126. George SJ, Lloyd CT, Angelini GD, Newby AC, Baker AH (2000) Inhibition of late vein graft neointima formation in human and porcine models by adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-3. Circulation 101:296–304PubMedGoogle Scholar
  127. Georgiadis D, Yiotakis A (2008) Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. Bioorg Med Chem 16:8781–8794CrossRefPubMedGoogle Scholar
  128. Geusens N, Hering L, Verlohren S, Luyten C, Drijkoningen K, Taube M, Vercruysse L, Hanssens M, Dechend R, Pijnenborg R (2010) Changes in endovascular trophoblast invasion and spiral artery remodelling at term in a transgenic preeclamptic rat model. Placenta 31:320–326CrossRefPubMedGoogle Scholar
  129. Gillespie DL, Patel A, Fileta B, Chang A, Barnes S, Flagg A, Kidwell M, Villavicencio JL, Rich NM (2002) Varicose veins possess greater quantities of MMP-1 than normal veins and demonstrate regional variation in MMP-1 and MMP-13. J Surg Res 106:233–238CrossRefPubMedGoogle Scholar
  130. Goerge T, Barg A, Schnaeker EM, Poppelmann B, Shpacovitch V, Rattenholl A, Maaser C, Luger TA, Steinhoff M, Schneider SW (2006) Tumor-derived matrix metalloproteinase-1 targets endothelial proteinase-activated receptor 1 promoting endothelial cell activation. Cancer Res 66:7766–7774CrossRefPubMedGoogle Scholar
  131. Goodall S, Crowther M, Hemingway DM, Bell PR, Thompson MM (2001) Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature of patients with abdominal aneurysms. Circulation 104:304–309PubMedGoogle Scholar
  132. Gooljarsingh LT, Lakdawala A, Coppo F, Luo L, Fields GB, Tummino PJ, Gontarek RR (2008) Characterization of an exosite binding inhibitor of matrix metalloproteinase 13. Protein Sci 17:66–71CrossRefPubMedGoogle Scholar
  133. Grams F, Brandstetter H, D’Alo S, Geppert D, Krell HW, Leinert H, Livi V, Menta E, Oliva A, Zimmermann G, Gram F, Livi VE (2001) Pyrimidine-2,4,6-Triones: a new effective and selective class of matrix metalloproteinase inhibitors. Biol Chem 382:1277–1285PubMedGoogle Scholar
  134. Grandas OH, Mountain DH, Kirkpatrick SS, Cassada DC, Stevens SL, Freeman MB, Goldman MH (2009) Regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases is mediated by estrogen and progesterone exposure. J Vasc Surg 49:185–191CrossRefPubMedGoogle Scholar
  135. Gross J, Lapiere CM (1962) Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci USA 48:1014–1022CrossRefPubMedGoogle Scholar
  136. Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA (2002) S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 297:1186–1190CrossRefPubMedGoogle Scholar
  137. Gu Z, Cui J, Brown S, Fridman R, Mobashery S, Strongin AY, Lipton SA (2005) A highly specific inhibitor of matrix metalloproteinase-9 rescues laminin from proteolysis and neurons from apoptosis in transient focal cerebral ischemia. J Neurosci 25:6401–6408CrossRefPubMedGoogle Scholar
  138. Guo YH, Gao W, Li Q, Li PF, Yao PY, Chen K (2004) Tissue inhibitor of metalloproteinases-4 suppresses vascular smooth muscle cell migration and induces cell apoptosis. Life Sci 75:2483–2493CrossRefPubMedGoogle Scholar
  139. Guo H, Lee JD, Uzui H, Toyoda K, Geshi T, Yue H, Ueda T (2005) Effects of copper and zinc on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells. Acta Cardiol 60:353–359CrossRefPubMedGoogle Scholar
  140. Guo RW, Yang LX, Wang H, Liu B, Wang L (2008) Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells. Regul Pept 147:37–44CrossRefPubMedGoogle Scholar
  141. Guo Z, Sun X, He Z, Jiang Y, Zhang X (2010) Role of matrix metalloproteinase-9 in apoptosis of hippocampal neurons in rats during early brain injury after subarachnoid hemorrhage. Neurol Sci 31:143–149CrossRefPubMedGoogle Scholar
  142. Gupta K, Shukla M, Cowland JB, Malemud CJ, Haqqi TM (2007) Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9. Arthritis Rheum 56:3326–3335CrossRefPubMedGoogle Scholar
  143. Hackmann AE, Rubin BG, Sanchez LA, Geraghty PA, Thompson RW, Curci JA (2008) A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair. J Vasc Surg 48:519–526, discussion 526CrossRefPubMedGoogle Scholar
  144. Hamilton JR, Nguyen PB, Cocks TM (1998) Atypical protease-activated receptor mediates endothelium-dependent relaxation of human coronary arteries. Circ Res 82:1306–1311PubMedGoogle Scholar
  145. Handsley MM, Edwards DR (2005) Metalloproteinases and their inhibitors in tumor angiogenesis. Int J Cancer 115:849–860CrossRefPubMedGoogle Scholar
  146. Hao L, Du M, Lopez-Campistrous A, Fernandez-Patron C (2004) Agonist-induced activation of matrix metalloproteinase-7 promotes vasoconstriction through the epidermal growth factor-receptor pathway. Circ Res 94:68–76CrossRefPubMedGoogle Scholar
  147. Haque NS, Fallon JT, Pan JJ, Taubman MB, Harpel PC (2004) Chemokine receptor-8 (CCR8) mediates human vascular smooth muscle cell chemotaxis and metalloproteinase-2 secretion. Blood 103:1296–1304CrossRefPubMedGoogle Scholar
  148. Harvey MB, Leco KJ, Arcellana-Panlilio MY, Zhang X, Edwards DR, Schultz GA (1995) Proteinase expression in early mouse embryos is regulated by leukaemia inhibitory factor and epidermal growth factor. Development 121:1005–1014PubMedGoogle Scholar
  149. Haviarova Z, Weismann P, Stvrtinova V, Benuska J (1999) The determination of the collagen and elastin amount in the human varicose vein by the computer morphometric method. Gen Physiol Biophys 18(Suppl 1):30–33PubMedGoogle Scholar
  150. Hawinkels LJ, Kuiper P, Wiercinska E, Verspaget HW, Liu Z, Pardali E, Sier CF, ten Dijke P (2010) Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis. Cancer Res 70:4141–4150CrossRefPubMedGoogle Scholar
  151. Heo SH, Choi YJ, Ryoo HM, Cho JY (2010) Expression profiling of ETS and MMP factors in VEGF-activated endothelial cells: role of MMP-10 in VEGF-induced angiogenesis. J Cell Physiol 224:734–742CrossRefPubMedGoogle Scholar
  152. Herman MP, Sukhova GK, Kisiel W, Foster D, Kehry MR, Libby P, Schonbeck U (2001) Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J Clin Invest 107:1117–1126CrossRefPubMedGoogle Scholar
  153. Herouy Y, May AE, Pornschlegel G, Stetter C, Grenz H, Preissner KT, Schopf E, Norgauer J, Vanscheidt W (1998) Lipodermatosclerosis is characterized by elevated expression and activation of matrix metalloproteinases: implications for venous ulcer formation. J Invest Dermatol 111:822–827CrossRefPubMedGoogle Scholar
  154. Herouy Y, Nockowski P, Schopf E, Norgauer J (1999) Lipodermatosclerosis and the significance of proteolytic remodeling in the pathogenesis of venous ulceration (Review). Int J Mol Med 3:511–515PubMedGoogle Scholar
  155. Higashi S, Miyazaki K (2003) Novel processing of beta-amyloid precursor protein catalyzed by membrane type 1 matrix metalloproteinase releases a fragment lacking the inhibitor domain against gelatinase A. Biochemistry 42:6514–6526CrossRefPubMedGoogle Scholar
  156. Hinterseher I, Bergert H, Kuhlisch E, Bloomenthal A, Pilarsky C, Ockert D, Schellong S, Saeger HD, Krex D (2006) Matrix metalloproteinase 2 polymorphisms in a caucasian population with abdominal aortic aneurysm. J Surg Res 133:121–128CrossRefPubMedGoogle Scholar
  157. Hoffman A, Qadri B, Frant J, Katz Y, Bhusare SR, Breuer E, Hadar R, Reich R (2008) Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastatic matrix metalloproteinase-2 selective inhibitor – synthesis and pharmacodynamic and pharmacokinetic analysis. J Med Chem 51:1406–1414CrossRefPubMedGoogle Scholar
  158. Hollenbeck ST, Sakakibara K, Faries PL, Workhu B, Liu B, Kent KC (2004) Stem cell factor and c-kit are expressed by and may affect vascular SMCs through an autocrine pathway. J Surg Res 120:288–294CrossRefPubMedGoogle Scholar
  159. Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, Mankani M, Robey PG, Poole AR, Pidoux I, Ward JM, Birkedal-Hansen H (1999) MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99:81–92CrossRefPubMedGoogle Scholar
  160. Hou P, Troen T, Ovejero MC, Kirkegaard T, Andersen TL, Byrjalsen I, Ferreras M, Sato T, Shapiro SD, Foged NT, Delaisse JM (2004) Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption. Bone 34:37–47CrossRefPubMedGoogle Scholar
  161. Hovsepian DM, Ziporin SJ, Sakurai MK, Lee JK, Curci JA, Thompson RW (2000) Elevated plasma levels of matrix metalloproteinase-9 in patients with abdominal aortic aneurysms: a circulating marker of degenerative aneurysm disease. J Vasc Interv Radiol 11:1345–1352CrossRefPubMedGoogle Scholar
  162. Hu Y, Xiang JS, DiGrandi MJ, Du X, Ipek M, Laakso LM, Li J, Li W, Rush TS, Schmid J, Skotnicki JS, Tam S, Thomason JR, Wang Q, Levin JI (2005) Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Bioorg Med Chem 13:6629–6644CrossRefPubMedGoogle Scholar
  163. Hurst DR, Schwartz MA, Jin Y, Ghaffari MA, Kozarekar P, Cao J, Sang QX (2005) Inhibition of enzyme activity of and cell-mediated substrate cleavage by membrane type 1 matrix metalloproteinase by newly developed mercaptosulphide inhibitors. Biochem J 392:527–536CrossRefPubMedGoogle Scholar
  164. Husslein H, Haider S, Meinhardt G, Prast J, Sonderegger S, Knofler M (2009) Expression, regulation and functional characterization of matrix metalloproteinase-3 of human trophoblast. Placenta 30:284–291CrossRefPubMedGoogle Scholar
  165. Huxley-Jones J, Clarke TK, Beck C, Toubaris G, Robertson DL, Boot-Handford RP (2007) The evolution of the vertebrate metzincins; insights from Ciona intestinalis and Danio rerio. BMC Evol Biol 7:63CrossRefPubMedGoogle Scholar
  166. Ikeda U, Shimada K (2003) Matrix metalloproteinases and coronary artery diseases. Clin Cardiol 26:55–59CrossRefPubMedGoogle Scholar
  167. Ikonomidis JS, Jones JA, Barbour JR, Stroud RE, Clark LL, Kaplan BS, Zeeshan A, Bavaria JE, Gorman JH 3rd, Spinale FG, Gorman RC (2007) Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valves. J Thorac Cardiovasc Surg 133:1028–1036CrossRefPubMedGoogle Scholar
  168. Ilic D, Almeida EA, Schlaepfer DD, Dazin P, Aizawa S, Damsky CH (1998) Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis. J Cell Biol 143:547–560CrossRefPubMedGoogle Scholar
  169. Imai K, Hiramatsu A, Fukushima D, Pierschbacher MD, Okada Y (1997) Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release. Biochem J 322(Pt 3):809–814PubMedGoogle Scholar
  170. Inoue S, Nakazawa T, Cho A, Dastvan F, Shilling D, Daum G, Reidy M (2007) Regulation of arterial lesions in mice depends on differential smooth muscle cell migration: a role for sphingosine-1-phosphate receptors. J Vasc Surg 46:756–763CrossRefPubMedGoogle Scholar
  171. Islam MM, Franco CD, Courtman DW, Bendeck MP (2003) A nonantibiotic chemically modified tetracycline (CMT-3) inhibits intimal thickening. Am J Pathol 163:1557–1566CrossRefPubMedGoogle Scholar
  172. Itoh Y, Takamura A, Ito N, Maru Y, Sato H, Suenaga N, Aoki T, Seiki M (2001) Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion. EMBO J 20:4782–4793CrossRefPubMedGoogle Scholar
  173. Jacob MP (2003) Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother 57:195–202CrossRefPubMedGoogle Scholar
  174. Jacob MP, Cazaubon M, Scemama A, Prie D, Blanchet F, Guillin MC, Michel JB (2002) Plasma matrix metalloproteinase-9 as a marker of blood stasis in varicose veins. Circulation 106:535–538CrossRefPubMedGoogle Scholar
  175. Jacob-Ferreira AL, Palei AC, Cau SB, Moreno H Jr, Martinez ML, Izidoro-Toledo TC, Gerlach RF, Tanus-Santos JE (2010) Evidence for the involvement of matrix metalloproteinases in the cardiovascular effects produced by nicotine. Eur J Pharmacol 627:216–222CrossRefPubMedGoogle Scholar
  176. Jacobsen FE, Lewis JA, Cohen SM (2006) A new role for old ligands: discerning chelators for zinc metalloproteinases. J Am Chem Soc 128:3156–3157CrossRefPubMedGoogle Scholar
  177. Jacobsen FE, Lewis JA, Cohen SM (2007) The design of inhibitors for medicinally relevant metalloproteins. ChemMedChem 2:152–171CrossRefPubMedGoogle Scholar
  178. Jacobsen J, Visse R, Sorensen HP, Enghild JJ, Brew K, Wewer UM, Nagase H (2008) Catalytic properties of ADAM12 and its domain deletion mutants. Biochemistry 47:537–547CrossRefPubMedGoogle Scholar
  179. Jacobsen JA, Major Jourden JL, Miller MT, Cohen SM (2010) To bind zinc or not to bind zinc: an examination of innovative approaches to improved metalloproteinase inhibition. Biochim Biophys Acta 1803:72–94CrossRefPubMedGoogle Scholar
  180. Jadhav V, Yamaguchi M, Obenaus A, Zhang JH (2008) Matrix metalloproteinase inhibition attenuates brain edema after surgical brain injury. Acta Neurochir Suppl 102:357–361CrossRefPubMedGoogle Scholar
  181. Jeyabalan A, Kerchner LJ, Fisher MC, McGuane JT, Doty KD, Conrad KP (2006) Matrix metalloproteinase-2 activity, protein, mRNA, and tissue inhibitors in small arteries from pregnant and relaxin-treated nonpregnant rats. J Appl Physiol 100:1955–1963CrossRefPubMedGoogle Scholar
  182. Jeyabalan A, Novak J, Doty KD, Matthews J, Fisher MC, Kerchner LJ, Conrad KP (2007) Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin. Endocrinology 148:189–197CrossRefPubMedGoogle Scholar
  183. Jin UH, Kang SK, Suh SJ, Hong SY, Park SD, Kim DW, Chang HW, Son JK, Lee SH, Son KH, Kim CH (2006a) Inhibitory effect of Salvia miltiorrhia BGE on matrix metalloproteinase-9 activity and migration of TNF-alpha-induced human aortic smooth muscle cells. Vascul Pharmacol 44:345–353CrossRefPubMedGoogle Scholar
  184. Jin X, Yagi M, Akiyama N, Hirosaki T, Higashi S, Lin CY, Dickson RB, Kitamura H, Miyazaki K (2006b) Matriptase activates stromelysin (MMP-3) and promotes tumor growth and angiogenesis. Cancer Sci 97:1327–1334CrossRefPubMedGoogle Scholar
  185. Jin UH, Suh SJ, Chang HW, Son JK, Lee SH, Son KH, Chang YC, Kim CH (2008) Tanshinone IIA from Salvia miltiorrhiza BUNGE inhibits human aortic smooth muscle cell migration and MMP-9 activity through AKT signaling pathway. J Cell Biochem 104:15–26CrossRefPubMedGoogle Scholar
  186. Johnson JL (2007) Matrix metalloproteinases: influence on smooth muscle cells and atherosclerotic plaque stability. Expert Rev Cardiovasc Ther 5:265–282CrossRefPubMedGoogle Scholar
  187. Johnson C, Galis ZS (2004) Matrix metalloproteinase-2 and -9 differentially regulate smooth muscle cell migration and cell-mediated collagen organization. Arterioscler Thromb Vasc Biol 24:54–60CrossRefPubMedGoogle Scholar
  188. Johnson JL, George SJ, Newby AC, Jackson CL (2005) Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Proc Natl Acad Sci USA 102:15575–15580CrossRefPubMedGoogle Scholar
  189. Johnson AR, Pavlovsky AG, Ortwine DF, Prior F, Man CF, Bornemeier DA, Banotai CA, Mueller WT, McConnell P, Yan C, Baragi V, Lesch C, Roark WH, Wilson M, Datta K, Guzman R, Han HK, Dyer RD (2007) Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J Biol Chem 282:27781–27791CrossRefPubMedGoogle Scholar
  190. Jones CB, Sane DC, Herrington DM (2003a) Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res 59:812–823CrossRefPubMedGoogle Scholar
  191. Jones GT, Phillips VL, Harris EL, Rossaak JI, van Rij AM (2003b) Functional matrix metalloproteinase-9 polymorphism (C-1562T) associated with abdominal aortic aneurysm. J Vasc Surg 38:1363–1367CrossRefPubMedGoogle Scholar
  192. Jones RL, Findlay JK, Salamonsen LA (2006) The role of activins during decidualisation of human endometrium. Aust N Z J Obstet Gynaecol 46:245–249CrossRefPubMedGoogle Scholar
  193. Jones JA, Ruddy JM, Bouges S, Zavadzkas JA, Brinsa TA, Stroud RE, Mukherjee R, Spinale FG, Ikonomidis JS (2010) Alterations in membrane type-1 matrix metalloproteinase abundance after the induction of thoracic aortic aneurysm in a murine model. Am J Physiol Heart Circ Physiol 299:H114–H124CrossRefPubMedGoogle Scholar
  194. Kadoglou NP, Daskalopoulou SS, Perrea D, Liapis CD (2005) Matrix metalloproteinases and diabetic vascular complications. Angiology 56:173–189CrossRefPubMedGoogle Scholar
  195. Kargiotis O, Chetty C, Gondi CS, Tsung AJ, Dinh DH, Gujrati M, Lakka SS, Kyritsis AP, Rao JS (2008) Adenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastoma. Oncogene 27:4830–4840CrossRefPubMedGoogle Scholar
  196. Kashiwagi M, Tortorella M, Nagase H, Brew K (2001) TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J Biol Chem 276:12501–12504CrossRefPubMedGoogle Scholar
  197. Kelly BA, Bond BC, Poston L (2003) Gestational profile of matrix metalloproteinases in rat uterine artery. Mol Hum Reprod 9:351–358CrossRefPubMedGoogle Scholar
  198. Kelly D, Cockerill G, Ng LL, Thompson M, Khan S, Samani NJ, Squire IB (2007) Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study. Eur Heart J 28:711–718CrossRefPubMedGoogle Scholar
  199. Kelly D, Khan SQ, Thompson M, Cockerill G, Ng LL, Samani N, Squire IB (2008) Plasma tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9: novel indicators of left ventricular remodelling and prognosis after acute myocardial infarction. Eur Heart J 29:2116–2124CrossRefPubMedGoogle Scholar
  200. Kenagy RD, Vergel S, Mattsson E, Bendeck M, Reidy MA, Clowes AW (1996) The role of plasminogen, plasminogen activators, and matrix metalloproteinases in primate arterial smooth muscle cell migration. Arterioscler Thromb Vasc Biol 16:1373–1382CrossRefPubMedGoogle Scholar
  201. Kerkela E, Bohling T, Herva R, Uria JA, Saarialho-Kere U (2001) Human macrophage metalloelastase (MMP-12) expression is induced in chondrocytes during fetal development and malignant transformation. Bone 29:487–493CrossRefPubMedGoogle Scholar
  202. Kester WR, Matthews BW (1977) Crystallographic study of the binding of dipeptide inhibitors to thermolysin: implications for the mechanism of catalysis. Biochemistry 16:2506–2516CrossRefPubMedGoogle Scholar
  203. Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, Brockbank SM, Edwards DR, Parker AE, Clark IM (2004) Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum 50:131–141CrossRefPubMedGoogle Scholar
  204. Khatri JJ, Johnson C, Magid R, Lessner SM, Laude KM, Dikalov SI, Harrison DG, Sung HJ, Rong Y, Galis ZS (2004) Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma. Circulation 109:520–525CrossRefPubMedGoogle Scholar
  205. Kim SH, Pudzianowski AT, Leavitt KJ, Barbosa J, McDonnell PA, Metzler WJ, Rankin BM, Liu R, Vaccaro W, Pitts W (2005) Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg Med Chem Lett 15:1101–1106CrossRefPubMedGoogle Scholar
  206. Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271:17124–17131CrossRefPubMedGoogle Scholar
  207. Kockx MM, Knaapen MW, Bortier HE, Cromheeke KM, Boutherin-Falson O, Finet M (1998) Vascular remodeling in varicose veins. Angiology 49:871–877CrossRefPubMedGoogle Scholar
  208. Koike Y, Shima F, Nakamizo A, Miyagi Y (2008) Direct localization of subthalamic nucleus supplemented by single-track electrophysiological guidance in deep brain stimulation lead implantation: techniques and clinical results. Stereotact Funct Neurosurg 86:173–178CrossRefPubMedGoogle Scholar
  209. Koskivirta I, Rahkonen O, Mayranpaa M, Pakkanen S, Husheem M, Sainio A, Hakovirta H, Laine J, Jokinen E, Vuorio E, Kovanen P, Jarvelainen H (2006) Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology. Histochem Cell Biol 126:335–342CrossRefPubMedGoogle Scholar
  210. Kosugi I, Urayama H, Kasashima F, Ohtake H, Watanabe Y (2003) Matrix metalloproteinase-9 and urokinase-type plasminogen activator in varicose veins. Ann Vasc Surg 17:234–238CrossRefPubMedGoogle Scholar
  211. Kowalewski R, Sobolewski K, Wolanska M, Gacko M (2004) Matrix metalloproteinases in the vein wall. Int Angiol 23:164–169PubMedGoogle Scholar
  212. Kruger A, Arlt MJ, Gerg M, Kopitz C, Bernardo MM, Chang M, Mobashery S, Fridman R (2005) Antimetastatic activity of a novel mechanism-based gelatinase inhibitor. Cancer Res 65:3523–3526CrossRefPubMedGoogle Scholar
  213. Kudo T, Takino T, Miyamori H, Thompson EW, Sato H (2007) Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels. Cancer Sci 98:563–568CrossRefPubMedGoogle Scholar
  214. Kwan JA, Schulze CJ, Wang W, Leon H, Sariahmetoglu M, Sung M, Sawicka J, Sims DE, Sawicki G, Schulz R (2004) Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro. FASEB J 18:690–692PubMedGoogle Scholar
  215. Lavee M, Goldman S, Daniel-Spiegel E, Shalev E (2009) Matrix metalloproteinase-2 is elevated in midtrimester amniotic fluid prior to the development of preeclampsia. Reprod Biol Endocrinol 7:85CrossRefPubMedGoogle Scholar
  216. Laviades C, Varo N, Fernandez J, Mayor G, Gil MJ, Monreal I, Diez J (1998) Abnormalities of the extracellular degradation of collagen type I in essential hypertension. Circulation 98:535–540PubMedGoogle Scholar
  217. Leco KJ, Waterhouse P, Sanchez OH, Gowing KL, Poole AR, Wakeham A, Mak TW, Khokha R (2001) Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3). J Clin Invest 108:817–829PubMedGoogle Scholar
  218. Ledgard AM, Lee RS, Peterson AJ (2009) Bovine endometrial legumain and TIMP-2 regulation in response to presence of a conceptus. Mol Reprod Dev 76:65–74CrossRefPubMedGoogle Scholar
  219. Ledour G, Moroy G, Rouffet M, Bourguet E, Guillaume D, Decarme M, Elmourabit H, Auge F, Alix AJ, Laronze JY, Bellon G, Hornebeck W, Sapi J (2008) Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with improved selectivity. Bioorg Med Chem 16:8745–8759CrossRefPubMedGoogle Scholar
  220. Lee M, Bernardo MM, Meroueh SO, Brown S, Fridman R, Mobashery S (2005) Synthesis of chiral 2-(4-phenoxyphenylsulfonylmethyl)thiiranes as selective gelatinase inhibitors. Org Lett 7:4463–4465CrossRefPubMedGoogle Scholar
  221. Lee M, Villegas-Estrada A, Celenza G, Boggess B, Toth M, Kreitinger G, Forbes C, Fridman R, Mobashery S, Chang M (2007) Metabolism of a highly selective gelatinase inhibitor generates active metabolite. Chem Biol Drug Des 70:371–382CrossRefPubMedGoogle Scholar
  222. Lee HY, You HJ, Won JY, Youn SW, Cho HJ, Park KW, Park WY, Seo JS, Park YB, Walsh K, Oh BH, Kim HS (2008) Forkhead factor, FOXO3a, induces apoptosis of endothelial cells through activation of matrix metalloproteinases. Arterioscler Thromb Vasc Biol 28:302–308CrossRefPubMedGoogle Scholar
  223. Lee M, Celenza G, Boggess B, Blase J, Shi Q, Toth M, Bernardo MM, Wolter WR, Suckow MA, Hesek D, Noll BC, Fridman R, Mobashery S, Chang M (2009a) A potent gelatinase inhibitor with anti-tumor-invasive activity and its metabolic disposition. Chem Biol Drug Des 73:189–202CrossRefPubMedGoogle Scholar
  224. Lee YH, Kim TY, Hong YM (2009b) Metalloproteinase-3 genotype as a predictor of cardiovascular risk in hypertensive adolescents. Korean Circ J 39:328–334CrossRefPubMedGoogle Scholar
  225. Lee YJ, Kim JS, Kang DG, Lee HS (2010) Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases. Exp Biol Med (Maywood) 235:247–255CrossRefGoogle Scholar
  226. Lemaitre V, O’Byrne TK, Borczuk AC, Okada Y, Tall AR, D’Armiento J (2001) ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. J Clin Invest 107:1227–1234CrossRefPubMedGoogle Scholar
  227. Lemaitre V, Soloway PD, D’Armiento J (2003) Increased medial degradation with pseudo-aneurysm formation in apolipoprotein E-knockout mice deficient in tissue inhibitor of metalloproteinases-1. Circulation 107:333–338CrossRefPubMedGoogle Scholar
  228. Levi E, Fridman R, Miao HQ, Ma YS, Yayon A, Vlodavsky I (1996) Matrix metalloproteinase 2 releases active soluble ectodomain of fibroblast growth factor receptor 1. Proc Natl Acad Sci USA 93:7069–7074CrossRefPubMedGoogle Scholar
  229. Levkau B, Kenagy RD, Karsan A, Weitkamp B, Clowes AW, Ross R, Raines EW (2002) Activation of metalloproteinases and their association with integrins: an auxiliary apoptotic pathway in human endothelial cells. Cell Death Differ 9:1360–1367CrossRefPubMedGoogle Scholar
  230. Li J, Rush TS 3rd, Li W, DeVincentis D, Du X, Hu Y, Thomason JR, Xiang JS, Skotnicki JS, Tam S, Cunningham KM, Chockalingam PS, Morris EA, Levin JI (2005) Synthesis and SAR of highly selective MMP-13 inhibitors. Bioorg Med Chem Lett 15:4961–4966CrossRefPubMedGoogle Scholar
  231. Li JJ, Nahra J, Johnson AR, Bunker A, O’Brien P, Yue WS, Ortwine DF, Man CF, Baragi V, Kilgore K, Dyer RD, Han HK (2008) Quinazolinones and pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. J Med Chem 51:835–841CrossRefPubMedGoogle Scholar
  232. Li W, Li J, Wu Y, Wu J, Hotchandani R, Cunningham K, McFadyen I, Bard J, Morgan P, Schlerman F, Xu X, Tam S, Goldman SJ, Williams C, Sypek J, Mansour TS (2009) A selective matrix metalloprotease 12 inhibitor for potential treatment of chronic obstructive pulmonary disease (COPD): discovery of (S)-2-(8-(methoxycarbonylamino)dibenzo[b, d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408). J Med Chem 52:1799–1802CrossRefPubMedGoogle Scholar
  233. Lijnen HR, Van Hoef B, Vanlinthout I, Verstreken M, Rio MC, Collen D (1999) Accelerated neointima formation after vascular injury in mice with stromelysin-3 (MMP-11) gene inactivation. Arterioscler Thromb Vasc Biol 19:2863–2870CrossRefPubMedGoogle Scholar
  234. Lin J, Davis HB, Dai Q, Chou YM, Craig T, Hinojosa-Laborde C, Lindsey ML (2008) Effects of early and late chronic pressure overload on extracellular matrix remodeling. Hypertens Res 31:1225–1231CrossRefPubMedGoogle Scholar
  235. Lindeman JH, Abdul-Hussien H, van Bockel JH, Wolterbeek R, Kleemann R (2009) Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm: doxycycline selectively depletes aortic wall neutrophils and cytotoxic T cells. Circulation 119:2209–2216CrossRefPubMedGoogle Scholar
  236. Lischper M, Beuck S, Thanabalasundaram G, Pieper C, Galla HJ (2010) Metalloproteinase mediated occludin cleavage in the cerebral microcapillary endothelium under pathological conditions. Brain Res 1326:114–127CrossRefPubMedGoogle Scholar
  237. Liu Z, Zhou X, Shapiro SD, Shipley JM, Twining SS, Diaz LA, Senior RM, Werb Z (2000) The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo. Cell 102:647–655CrossRefPubMedGoogle Scholar
  238. Liu G, Zhang X, Lin H, Li Q, Wang H, Ni J, Amy Sang QX, Zhu C (2005) Expression of matrix metalloproteinase-26 (MMP-26) mRNA in mouse uterus during the estrous cycle and early pregnancy. Life Sci 77:3355–3365CrossRefPubMedGoogle Scholar
  239. Lohi J, Wilson CL, Roby JD, Parks WC (2001) Epilysin, a novel human matrix metalloproteinase (MMP-28) expressed in testis and keratinocytes and in response to injury. J Biol Chem 276:10134–10144CrossRefPubMedGoogle Scholar
  240. Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT (2002) Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 110:625–632PubMedGoogle Scholar
  241. Lopez-Candales A, Holmes DR, Liao S, Scott MJ, Wickline SA, Thompson RW (1997) Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms. Am J Pathol 150:993–1007PubMedGoogle Scholar
  242. Louboutin JP, Agrawal L, Reyes BA, Van Bockstaele EJ, Strayer DS (2010) HIV-1 gp120-induced injury to the blood-brain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stress. J Neuropathol Exp Neurol 69:801–816CrossRefPubMedGoogle Scholar
  243. Lovdahl C, Thyberg J, Hultgardh-Nilsson A (2000) The synthetic metalloproteinase inhibitor batimastat suppresses injury-induced phosphorylation of MAP kinase ERK1/ERK2 and phenotypic modification of arterial smooth muscle cells in vitro. J Vasc Res 37:345–354CrossRefPubMedGoogle Scholar
  244. Lovejoy B, Hassell AM, Luther MA, Weigl D, Jordan SR (1994) Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself. Biochemistry 33:8207–8217CrossRefPubMedGoogle Scholar
  245. Lovejoy B, Welch AR, Carr S, Luong C, Broka C, Hendricks RT, Campbell JA, Walker KA, Martin R, Van Wart H, Browner MF (1999) Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors. Nat Struct Biol 6:217–221CrossRefPubMedGoogle Scholar
  246. Lucchesi PA, Sabri A, Belmadani S, Matrougui K (2004) Involvement of metalloproteinases 2/9 in epidermal growth factor receptor transactivation in pressure-induced myogenic tone in mouse mesenteric resistance arteries. Circulation 110:3587–3593CrossRefPubMedGoogle Scholar
  247. Luttun A, Lutgens E, Manderveld A, Maris K, Collen D, Carmeliet P, Moons L (2004) Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth. Circulation 109:1408–1414CrossRefPubMedGoogle Scholar
  248. Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R (2001) Proteinase-activated receptors. Pharmacol Rev 53:245–282PubMedGoogle Scholar
  249. Malik MT, Kakar SS (2006) Regulation of angiogenesis and invasion by human Pituitary tumor transforming gene (PTTG) through increased expression and secretion of matrix metalloproteinase-2 (MMP-2). Mol Cancer 5:61CrossRefPubMedGoogle Scholar
  250. Manes S, Mira E, Barbacid MM, Cipres A, Fernandez-Resa P, Buesa JM, Merida I, Aracil M, Marquez G, Martinez AC (1997) Identification of insulin-like growth factor-binding protein-1 as a potential physiological substrate for human stromelysin-3. J Biol Chem 272:25706–25712CrossRefPubMedGoogle Scholar
  251. Mannello F, Luchetti F, Falcieri E, Papa S (2005) Multiple roles of matrix metalloproteinases during apoptosis. Apoptosis 10:19–24CrossRefPubMedGoogle Scholar
  252. Manning MW, Cassis LA, Daugherty A (2003) Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 23:483–488CrossRefPubMedGoogle Scholar
  253. Manzetti S, McCulloch DR, Herington AC, van der Spoel D (2003) Modeling of enzyme-substrate complexes for the metalloproteases MMP-3, ADAM-9 and ADAM-10. J Comput Aided Mol Des 17:551–565CrossRefPubMedGoogle Scholar
  254. Maquoi E, Sounni NE, Devy L, Olivier F, Frankenne F, Krell HW, Grams F, Foidart JM, Noel A (2004) Anti-invasive, antitumoral, and antiangiogenic efficacy of a pyrimidine-2,4,6-trione derivative, an orally active and selective matrix metalloproteinases inhibitor. Clin Cancer Res 10:4038–4047CrossRefPubMedGoogle Scholar
  255. Marchenko GN, Strongin AY (2001) MMP-28, a new human matrix metalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors. Gene 265:87–93CrossRefPubMedGoogle Scholar
  256. Marchenko ND, Marchenko GN, Weinreb RN, Lindsey JD, Kyshtoobayeva A, Crawford HC, Strongin AY (2004) Beta-catenin regulates the gene of MMP-26, a novel metalloproteinase expressed both in carcinomas and normal epithelial cells. Int J Biochem Cell Biol 36:942–956CrossRefPubMedGoogle Scholar
  257. Matsumura S, Iwanaga S, Mochizuki S, Okamoto H, Ogawa S, Okada Y (2005) Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice. J Clin Invest 115:599–609PubMedGoogle Scholar
  258. Matziari M, Beau F, Cuniasse P, Dive V, Yiotakis A (2004) Evaluation of P1′-diversified phosphinic peptides leads to the development of highly selective inhibitors of MMP-11. J Med Chem 47:325–336CrossRefPubMedGoogle Scholar
  259. Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111:649–658PubMedGoogle Scholar
  260. McQuibban GA, Butler GS, Gong JH, Bendall L, Power C, Clark-Lewis I, Overall CM (2001) Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J Biol Chem 276:43503–43508CrossRefPubMedGoogle Scholar
  261. Mendez MV, Raffetto JD, Phillips T, Menzoian JO, Park HY (1999) The proliferative capacity of neonatal skin fibroblasts is reduced after exposure to venous ulcer wound fluid: a potential mechanism for senescence in venous ulcers. J Vasc Surg 30:734–743CrossRefPubMedGoogle Scholar
  262. Merchant SJ, Davidge ST (2004) The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia. BJOG 111:931–939CrossRefPubMedGoogle Scholar
  263. Michaelides MR, Dellaria JF, Gong J, Holms JH, Bouska JJ, Stacey J, Wada CK, Heyman HR, Curtin ML, Guo Y, Goodfellow CL, Elmore IB, Albert DH, Magoc TJ, Marcotte PA, Morgan DW, Davidsen SK (2001) Biaryl ether retrohydroxamates as potent, long-lived, orally bioavailable MMP inhibitors. Bioorg Med Chem Lett 11:1553–1556CrossRefPubMedGoogle Scholar
  264. Milner JM, Cawston TE (2005) Matrix metalloproteinase knockout studies and the potential use of matrix metalloproteinase inhibitors in the rheumatic diseases. Curr Drug Targets Inflamm Allergy 4:363–375CrossRefPubMedGoogle Scholar
  265. Mimura T, Han KY, Onguchi T, Chang JH, Kim TI, Kojima T, Zhou Z, Azar DT (2009) MT1-MMP-mediated cleavage of decorin in corneal angiogenesis. J Vasc Res 46:541–550CrossRefPubMedGoogle Scholar
  266. Mishra B, Kizaki K, Koshi K, Ushizawa K, Takahashi T, Hosoe M, Sato T, Ito A, Hashizume K (2010) Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its related extracellular matrix degrading enzymes in the endometrium during estrous cycle and early gestation in cattle. Reprod Biol Endocrinol 8:60CrossRefPubMedGoogle Scholar
  267. Mix KS, Coon CI, Rosen ED, Suh N, Sporn MB, Brinckerhoff CE (2004) Peroxisome proliferator-activated receptor-gamma-independent repression of collagenase gene expression by 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and prostaglandin 15-deoxy-delta(12,14) J2: a role for Smad signaling. Mol Pharmacol 65:309–318CrossRefPubMedGoogle Scholar
  268. Moller MN, Werther K, Nalla A, Stangerup SE, Thomsen J, Bog-Hansen TC (2010) Nielsen HJ and Caye-Thomasen P Angiogenesis in vestibular schwannomas: expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1. Laryngoscope 120:657–662CrossRefPubMedGoogle Scholar
  269. Momohara S, Okamoto H, Komiya K, Ikari K, Takeuchi M, Tomatsu T, Kamatani N (2004) Matrix metalloproteinase 28/epilysin expression in cartilage from patients with rheumatoid arthritis and osteoarthritis: comment on the article by Kevorkian et al. Arthritis Rheum 50:4074–4075, author reply 4075CrossRefPubMedGoogle Scholar
  270. Montagnana M, Lippi G, Albiero A, Scevarolli S, Salvagno GL, Franchi M, Guidi GC (2009) Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre-eclamptic pregnancy. J Clin Lab Anal 23:88–92CrossRefPubMedGoogle Scholar
  271. Morales R, Perrier S, Florent JM, Beltra J, Dufour S, De Mendez I, Manceau P, Tertre A, Moreau F, Compere D, Dublanchet AC, O’Gara M (2004) Crystal structures of novel non-peptidic, non-zinc chelating inhibitors bound to MMP-12. J Mol Biol 341:1063–1076CrossRefPubMedGoogle Scholar
  272. Morla AO, Mogford JE (2000) Control of smooth muscle cell proliferation and phenotype by integrin signaling through focal adhesion kinase. Biochem Biophys Res Commun 272:298–302CrossRefPubMedGoogle Scholar
  273. Morrison JF, Walsh CT (1988) The behavior and significance of slow-binding enzyme inhibitors. Adv Enzymol Relat Areas Mol Biol 61:201–301PubMedGoogle Scholar
  274. Mosorin M, Juvonen J, Biancari F, Satta J, Surcel HM, Leinonen M, Saikku P, Juvonen T (2001) Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study. J Vasc Surg 34:606–610CrossRefPubMedGoogle Scholar
  275. Moss ML, Sklair-Tavron L, Nudelman R (2008) Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nat Clin Pract Rheumatol 4:300–309CrossRefPubMedGoogle Scholar
  276. Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564CrossRefPubMedGoogle Scholar
  277. Mott JD, Thomas CL, Rosenbach MT, Takahara K, Greenspan DS, Banda MJ (2000) Post-translational proteolytic processing of procollagen C-terminal proteinase enhancer releases a metalloproteinase inhibitor. J Biol Chem 275:1384–1390CrossRefPubMedGoogle Scholar
  278. Mulvany MJ, Baumbach GL, Aalkjaer C, Heagerty AM, Korsgaard N, Schiffrin EL, Heistad DD (1996) Vascular remodeling. Hypertension 28:505–506PubMedGoogle Scholar
  279. Murphy G, Nagase H (2008) Progress in matrix metalloproteinase research. Mol Aspects Med 29:290–308CrossRefPubMedGoogle Scholar
  280. Murphy G, Houbrechts A, Cockett MI, Williamson RA, O’Shea M, Docherty AJ (1991) The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity. Biochemistry 30:8097–8102CrossRefPubMedGoogle Scholar
  281. Mwaura B, Mahendran B, Hynes N, Defreitas D, Avalos G, Adegbola T, Adham M, Connolly CE, Sultan S (2006) The impact of differential expression of extracellular matrix metalloproteinase inducer, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2 and PDGF-AA on the chronicity of venous leg ulcers. Eur J Vasc Endovasc Surg 31:306–310CrossRefPubMedGoogle Scholar
  282. Myers JE, Merchant SJ, Macleod M, Mires GJ, Baker PN, Davidge ST (2005) MMP-2 levels are elevated in the plasma of women who subsequently develop preeclampsia. Hypertens Pregnancy 24:103–115CrossRefPubMedGoogle Scholar
  283. Nagareddy PR, Chow FL, Hao L, Wang X, Nishimura T, MacLeod KM, McNeill JH, Fernandez-Patron C (2009) Maintenance of adrenergic vascular tone by MMP transactivation of the EGFR requires PI3K and mitochondrial ATP synthesis. Cardiovasc Res 84:368–377CrossRefPubMedGoogle Scholar
  284. Nagareddy PR, MacLeod KM, McNeill JH (2010) GPCR agonist-induced transactivation of the EGFR upregulates MLC II expression and promotes hypertension in insulin-resistant rats. Cardiovasc Res 87:177–186CrossRefPubMedGoogle Scholar
  285. Nagase H, Fushimi K (2008) Elucidating the function of non catalytic domains of collagenases and aggrecanases. Connect Tissue Res 49:169–174CrossRefPubMedGoogle Scholar
  286. Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573CrossRefPubMedGoogle Scholar
  287. Nagashima H, Aoka Y, Sakomura Y, Sakuta A, Aomi S, Ishizuka N, Hagiwara N, Kawana M, Kasanuki H (2002) A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, cerivastatin, suppresses production of matrix metalloproteinase-9 in human abdominal aortic aneurysm wall. J Vasc Surg 36:158–163CrossRefPubMedGoogle Scholar
  288. Nakatani S, Ikura M, Yamamoto S, Nishita Y, Itadani S, Habashita H, Sugiura T, Ogawa K, Ohno H, Takahashi K, Nakai H, Toda M (2006) Design and synthesis of novel metalloproteinase inhibitors. Bioorg Med Chem 14:5402–5422CrossRefPubMedGoogle Scholar
  289. Narumiya H, Zhang Y, Fernandez-Patron C, Guilbert LJ, Davidge ST (2001) Matrix metalloproteinase-2 is elevated in the plasma of women with preeclampsia. Hypertens Pregnancy 20:185–194CrossRefPubMedGoogle Scholar
  290. Naruse K, Lash GE, Innes BA, Otun HA, Searle RF, Robson SC, Bulmer JN (2009) Localization of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors for MMPs (TIMPs) in uterine natural killer cells in early human pregnancy. Hum Reprod 24:553–561CrossRefPubMedGoogle Scholar
  291. Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303:1483–1487CrossRefPubMedGoogle Scholar
  292. Newby AC (2005) Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 85:1–31CrossRefPubMedGoogle Scholar
  293. Newsome AL, Johnson JP, Seipelt RL, Thompson MW (2007) Apolactoferrin inhibits the catalytic domain of matrix metalloproteinase-2 by zinc chelation. Biochem Cell Biol 85:563–572CrossRefPubMedGoogle Scholar
  294. Noe V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM, Mareel M (2001) Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci 114:111–118PubMedGoogle Scholar
  295. Norgauer J, Hildenbrand T, Idzko M, Panther E, Bandemir E, Hartmann M, Vanscheidt W, Herouy Y (2002) Elevated expression of extracellular matrix metalloproteinase inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers. Br J Dermatol 147:1180–1186CrossRefPubMedGoogle Scholar
  296. Nuti E, Tuccinardi T, Rossello A (2007) Matrix metalloproteinase inhibitors: new challenges in the era of post broad-spectrum inhibitors. Curr Pharm Des 13:2087–2100CrossRefPubMedGoogle Scholar
  297. Ogata Y, Enghild JJ, Nagase H (1992) Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 267:3581–3584PubMedGoogle Scholar
  298. Oh C, Dong Y, Liu H, Thompson LP (2008) Intrauterine hypoxia upregulates proinflammatory cytokines and matrix metalloproteinases in fetal guinea pig hearts. Am J Obstet Gynecol 199(78):e71–e76Google Scholar
  299. Ohuchi E, Imai K, Fujii Y, Sato H, Seiki M, Okada Y (1997) Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem 272:2446–2451CrossRefPubMedGoogle Scholar
  300. Okamoto T, Akaike T, Nagano T, Miyajima S, Suga M, Ando M, Ichimori K, Maeda H (1997) Activation of human neutrophil procollagenase by nitrogen dioxide and peroxynitrite: a novel mechanism for procollagenase activation involving nitric oxide. Arch Biochem Biophys 342:261–274CrossRefPubMedGoogle Scholar
  301. Olson MW, Toth M, Gervasi DC, Sado Y, Ninomiya Y, Fridman R (1998) High affinity binding of latent matrix metalloproteinase-9 to the alpha2(IV) chain of collagen IV. J Biol Chem 273:10672–10681CrossRefPubMedGoogle Scholar
  302. Onal IK, Altun B, Onal ED, Kirkpantur A, Gul Oz S, Turgan C (2009) Serum levels of MMP-9 and TIMP-1 in primary hypertension and effect of antihypertensive treatment. Eur J Intern Med 20:369–372CrossRefPubMedGoogle Scholar
  303. Onaran MB, Comeau AB, Seto CT (2005) Squaric acid-based peptidic inhibitors of matrix metalloprotease-1. J Org Chem 70:10792–10802CrossRefPubMedGoogle Scholar
  304. Ozerdem U, Mach-Hofacre B, Varki N, Folberg R, Mueller AJ, Ochabski R, Pham T, Appelt K, Freeman WR (2002) The effect of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinases, on uveal melanoma rabbit model. Curr Eye Res 24:86–91CrossRefPubMedGoogle Scholar
  305. Ozkok E, Aydin M, Babalik E, Ozbek Z, Ince N, Kara I (2008) Combined impact of matrix metalloproteinase-3 and paraoxonase 1 55/192 gene variants on coronary artery disease in Turkish patients. Med Sci Monit 14:CR536–CR542PubMedGoogle Scholar
  306. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8:221–233CrossRefPubMedGoogle Scholar
  307. Palei AC, Sandrim VC, Cavalli RC, Tanus-Santos JE (2008) Comparative assessment of matrix metalloproteinase (MMP)-2 and MMP-9, and their inhibitors, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in preeclampsia and gestational hypertension. Clin Biochem 41:875–880CrossRefPubMedGoogle Scholar
  308. Palei AC, Sandrim VC, Duarte G, Cavalli RC, Gerlach RF, Tanus-Santos JE (2010) Matrix metalloproteinase (MMP)-9 genotypes and haplotypes in preeclampsia and gestational hypertension. Clin Chim Acta 411:874–877CrossRefPubMedGoogle Scholar
  309. Park HI, Ni J, Gerkema FE, Liu D, Belozerov VE, Sang QX (2000) Identification and characterization of human endometase (Matrix metalloproteinase-26) from endometrial tumor. J Biol Chem 275:20540–20544CrossRefPubMedGoogle Scholar
  310. Parks WC, Wilson CL, Lopez-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629CrossRefPubMedGoogle Scholar
  311. Parra JR, Cambria RA, Hower CD, Dassow MS, Freischlag JA, Seabrook GR, Towne JB (1998) Tissue inhibitor of metalloproteinase-1 is increased in the saphenofemoral junction of patients with varices in the leg. J Vasc Surg 28:669–675CrossRefPubMedGoogle Scholar
  312. Pascarella L, Penn A, Schmid-Schonbein GW (2005) Venous hypertension and the inflammatory cascade: major manifestations and trigger mechanisms. Angiology 56(Suppl 1):S3–S10CrossRefPubMedGoogle Scholar
  313. Patterson ML, Atkinson SJ, Knauper V, Murphy G (2001) Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain. FEBS Lett 503:158–162CrossRefPubMedGoogle Scholar
  314. Pawlak K, Pawlak D, Mysliwiec M (2008) Urokinase-type plasminogen activator and metalloproteinase-2 are independently related to the carotid atherosclerosis in haemodialysis patients. Thromb Res 121:543–548CrossRefPubMedGoogle Scholar
  315. Pei D, Weiss SJ (1995) Furin-dependent intracellular activation of the human stromelysin-3 zymogen. Nature 375:244–247CrossRefPubMedGoogle Scholar
  316. Pei D, Kang T, Qi H (2000) Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation. J Biol Chem 275:33988–33997CrossRefPubMedGoogle Scholar
  317. Pendas AM, Folgueras AR, Llano E, Caterina J, Frerard F, Rodriguez F, Astudillo A, Noel A, Birkedal-Hansen H, Lopez-Otin C (2004) Diet-induced obesity and reduced skin cancer susceptibility in matrix metalloproteinase 19-deficient mice. Mol Cell Biol 24:5304–5313CrossRefPubMedGoogle Scholar
  318. Pepper MS (2001) Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21:1104–1117CrossRefPubMedGoogle Scholar
  319. Petersen E, Gineitis A, Wagberg F, Angquist KA (2000) Activity of matrix metalloproteinase-2 and -9 in abdominal aortic aneurysms. Relation to size and rupture. Eur J Vasc Endovasc Surg 20:457–461CrossRefPubMedGoogle Scholar
  320. Pochetti G, Gavuzzo E, Campestre C, Agamennone M, Tortorella P, Consalvi V, Gallina C, Hiller O, Tschesche H, Tucker PA, Mazza F (2006) Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates. J Med Chem 49:923–931CrossRefPubMedGoogle Scholar
  321. Pochetti G, Montanari R, Gege C, Chevrier C, Taveras AG, Mazza F (2009) Extra binding region induced by non-zinc chelating inhibitors into the S1′ subsite of matrix metalloproteinase 8 (MMP-8). J Med Chem 52:1040–1049CrossRefPubMedGoogle Scholar
  322. Poon LC, Nekrasova E, Anastassopoulos P, Livanos P, Nicolaides KH (2009) First-trimester maternal serum matrix metalloproteinase-9 (MMP-9) and adverse pregnancy outcome. Prenat Diagn 29:553–559CrossRefPubMedGoogle Scholar
  323. Poon LC, Akolekar R, Lachmann R, Beta J, Nicolaides KH (2010) Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11-13 weeks. Ultrasound Obstet Gynecol 35:662–670PubMedGoogle Scholar
  324. Prescott MF, Sawyer WK, Von Linden-Reed J, Jeune M, Chou M, Caplan SL, Jeng AY (1999) Effect of matrix metalloproteinase inhibition on progression of atherosclerosis and aneurysm in LDL receptor-deficient mice overexpressing MMP-3, MMP-12, and MMP-13 and on restenosis in rats after balloon injury. Ann N Y Acad Sci 878:179–190CrossRefPubMedGoogle Scholar
  325. Price A, Shi Q, Morris D, Wilcox ME, Brasher PM, Rewcastle NB, Shalinsky D, Zou H, Appelt K, Johnston RN, Yong VW, Edwards D, Forsyth P (1999) Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340. Clin Cancer Res 5:845–854PubMedGoogle Scholar
  326. Puerta DT, Cohen SM (2003) Examination of novel zinc-binding groups for use in matrix metalloproteinase inhibitors. Inorg Chem 42:3423–3430CrossRefPubMedGoogle Scholar
  327. Puerta DT, Lewis JA, Cohen SM (2004) New beginnings for matrix metalloproteinase inhibitors: identification of high-affinity zinc-binding groups. J Am Chem Soc 126:8388–8389CrossRefPubMedGoogle Scholar
  328. Puerta DT, Mongan J, Tran BL, McCammon JA, Cohen SM (2005) Potent, selective pyrone-based inhibitors of stromelysin-1. J Am Chem Soc 127:14148–14149CrossRefPubMedGoogle Scholar
  329. Puerta DT, Griffin MO, Lewis JA, Romero-Perez D, Garcia R, Villarreal FJ, Cohen SM (2006) Heterocyclic zinc-binding groups for use in next-generation matrix metalloproteinase inhibitors: potency, toxicity, and reactivity. J Biol Inorg Chem 11:131–138CrossRefPubMedGoogle Scholar
  330. Pyo R, Lee JK, Shipley JM, Curci JA, Mao D, Ziporin SJ, Ennis TL, Shapiro SD, Senior RM, Thompson RW (2000) Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest 105:1641–1649CrossRefPubMedGoogle Scholar
  331. Raffetto JD, Khalil RA (2008) Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 75:346–359CrossRefPubMedGoogle Scholar
  332. Raffetto JD, Mendez MV, Marien BJ, Byers HR, Phillips TJ, Park HY, Menzoian JO (2001) Changes in cellular motility and cytoskeletal actin in fibroblasts from patients with chronic venous insufficiency and in neonatal fibroblasts in the presence of chronic wound fluid. J Vasc Surg 33:1233–1241CrossRefPubMedGoogle Scholar
  333. Raffetto JD, Vasquez R, Goodwin DG, Menzoian JO (2006) Mitogen-activated protein kinase pathway regulates cell proliferation in venous ulcer fibroblasts. Vasc Endovascular Surg 40:59–66CrossRefPubMedGoogle Scholar
  334. Raffetto JD, Ross RL, Khalil RA (2007) Matrix metalloproteinase 2-induced venous dilation via hyperpolarization and activation of K+ channels: relevance to varicose vein formation. J Vasc Surg 45:373–380CrossRefPubMedGoogle Scholar
  335. Rao BG (2005) Recent developments in the design of specific Matrix Metalloproteinase inhibitors aided by structural and computational studies. Curr Pharm Des 11:295–322CrossRefPubMedGoogle Scholar
  336. Rauch I, Iglseder B, Paulweber B, Ladurner G, Strasser P (2008) MMP-9 haplotypes and carotid artery atherosclerosis: an association study introducing a novel multicolour multiplex RealTime PCR protocol. Eur J Clin Invest 38:24–33CrossRefPubMedGoogle Scholar
  337. Ravanti L, Kahari VM (2000) Matrix metalloproteinases in wound repair (review). Int J Mol Med 6:391–407PubMedGoogle Scholar
  338. Razavian M, Zhang J, Nie L, Tavakoli S, Razavian N, Dobrucki LW, Sinusas AJ, Edwards DS (2010) Azure M and Sadeghi MM Molecular imaging of matrix metalloproteinase activation to predict murine aneurysm expansion in vivo. J Nucl Med 51:1107–1115CrossRefPubMedGoogle Scholar
  339. Reister F, Kingdom JC, Ruck P, Marzusch K, Heyl W, Pauer U, Kaufmann P, Rath W, Huppertz B (2006) Altered protease expression by periarterial trophoblast cells in severe early-onset preeclampsia with IUGR. J Perinat Med 34:272–279CrossRefPubMedGoogle Scholar
  340. Reiter LA, Freeman-Cook KD, Jones CS, Martinelli GJ, Antipas AS, Berliner MA, Datta K, Downs JT, Eskra JD, Forman MD, Greer EM, Guzman R, Hardink JR, Janat F, Keene NF, Laird ER, Liras JL, Lopresti-Morrow LL, Mitchell PG, Pandit J, Robertson D, Sperger D, Vaughn-Bowser ML, Waller DM, Yocum SA (2006) Potent, selective pyrimidinetrione-based inhibitors of MMP-13. Bioorg Med Chem Lett 16:5822–5826CrossRefPubMedGoogle Scholar
  341. Renkiewicz R, Qiu L, Lesch C, Sun X, Devalaraja R, Cody T, Kaldjian E, Welgus H, Baragi V (2003) Broad-spectrum matrix metalloproteinase inhibitor marimastat-induced musculoskeletal side effects in rats. Arthritis Rheum 48:1742–1749CrossRefPubMedGoogle Scholar
  342. Rodriguez JA, Orbe J, Martinez de Lizarrondo S, Calvayrac O, Rodriguez C, Martinez-Gonzalez J, Paramo JA (2008) Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli. Front Biosci 13:2916–2921CrossRefPubMedGoogle Scholar
  343. Rodriguez-Manzaneque JC, Westling J, Thai SN, Luque A, Knauper V, Murphy G, Sandy JD, Iruela-Arispe ML (2002) ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitors. Biochem Biophys Res Commun 293:501–508CrossRefPubMedGoogle Scholar
  344. Roman-Garcia P, Coto E, Reguero JR, Cannata-Andia JB, Lozano I, Avanzas P, Moris C, Rodriguez I (2009) Matrix metalloproteinase 1 promoter polymorphisms and risk of myocardial infarction: a case-control study in a Spanish population. Coron Artery Dis 20:383–386CrossRefPubMedGoogle Scholar
  345. Romero-Perez D, Fricovsky E, Yamasaki KG, Griffin M, Barraza-Hidalgo M, Dillmann W, Villarreal F (2008) Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection. J Am Coll Cardiol 52:1086–1094CrossRefPubMedGoogle Scholar
  346. Rossello A, Nuti E, Catalani MP, Carelli P, Orlandini E, Rapposelli S, Tuccinardi T, Atkinson SJ, Murphy G, Balsamo A (2005) A new development of matrix metalloproteinase inhibitors: twin hydroxamic acids as potent inhibitors of MMPs. Bioorg Med Chem Lett 15:2311–2314CrossRefPubMedGoogle Scholar
  347. Rouis M, Adamy C, Duverger N, Lesnik P, Horellou P, Moreau M, Emmanuel F, Caillaud JM, Laplaud PM, Dachet C, Chapman MJ (1999) Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice. Circulation 100:533–540PubMedGoogle Scholar
  348. Rozanov DV, Ghebrehiwet B, Postnova TI, Eichinger A, Deryugina EI, Strongin AY (2002) The hemopexin-like C-terminal domain of membrane type 1 matrix metalloproteinase regulates proteolysis of a multifunctional protein, gC1qR. J Biol Chem 277:9318–9325CrossRefPubMedGoogle Scholar
  349. Ruiz S, Henschen-Edman AH, Nagase H, Tenner AJ (1999) Digestion of C1q collagen-like domain with MMPs-1,-2,-3, and -9 further defines the sequence involved in the stimulation of neutrophil superoxide production. J Leukoc Biol 66:416–422PubMedGoogle Scholar
  350. Rundhaug JE (2005) Matrix metalloproteinases and angiogenesis. J Cell Mol Med 9:267–285CrossRefPubMedGoogle Scholar
  351. Ryu OH, Fincham AG, Hu CC, Zhang C, Qian Q, Bartlett JD, Simmer JP (1999) Characterization of recombinant pig enamelysin activity and cleavage of recombinant pig and mouse amelogenins. J Dent Res 78:743–750CrossRefPubMedGoogle Scholar
  352. Saarialho-Kere U, Kerkela E, Jahkola T, Suomela S, Keski-Oja J, Lohi J (2002) Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair. J Invest Dermatol 119:14–21CrossRefPubMedGoogle Scholar
  353. Sadowski T, Dietrich S, Koschinsky F, Sedlacek R (2003a) Matrix metalloproteinase 19 regulates insulin-like growth factor-mediated proliferation, migration, and adhesion in human keratinocytes through proteolysis of insulin-like growth factor binding protein-3. Mol Biol Cell 14:4569–4580CrossRefPubMedGoogle Scholar
  354. Sadowski T, Dietrich S, Muller M, Havlickova B, Schunck M, Proksch E, Muller MS, Sedlacek R (2003b) Matrix metalloproteinase-19 expression in normal and diseased skin: dysregulation by epidermal proliferation. J Invest Dermatol 121:989–996CrossRefPubMedGoogle Scholar
  355. Sadowski T, Dietrich S, Koschinsky F, Ludwig A, Proksch E, Titz B, Sedlacek R (2005) Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration. Cell Mol Life Sci 62:870–880CrossRefPubMedGoogle Scholar
  356. Sakalihasan N, Delvenne P, Nusgens BV, Limet R, Lapiere CM (1996) Activated forms of MMP2 and MMP9 in abdominal aortic aneurysms. J Vasc Surg 24:127–133CrossRefPubMedGoogle Scholar
  357. Sangiorgi G, D’Averio R, Mauriello A, Bondio M, Pontillo M, Castelvecchio S, Trimarchi S, Tolva V, Nano G, Rampoldi V, Spagnoli LG, Inglese L (2001) Plasma levels of metalloproteinases-3 and -9 as markers of successful abdominal aortic aneurysm exclusion after endovascular graft treatment. Circulation 104:I288–I295CrossRefPubMedGoogle Scholar
  358. Sansilvestri-Morel P, Fioretti F, Rupin A, Senni K, Fabiani JN, Godeau G, Verbeuren TJ (2007) Comparison of extracellular matrix in skin and saphenous veins from patients with varicose veins: does the skin reflect venous matrix changes? Clin Sci (Lond) 112:229–239CrossRefGoogle Scholar
  359. Savani RC, Wang C, Yang B, Zhang S, Kinsella MG, Wight TN, Stern R, Nance DM, Turley EA (1995) Migration of bovine aortic smooth muscle cells after wounding injury. The role of hyaluronan and RHAMM. J Clin Invest 95:1158–1168CrossRefPubMedGoogle Scholar
  360. Sawicki G, Radomski MW, Winkler-Lowen B, Krzymien A, Guilbert LJ (2000) Polarized release of matrix metalloproteinase-2 and -9 from cultured human placental syncytiotrophoblasts. Biol Reprod 63:1390–1395CrossRefPubMedGoogle Scholar
  361. Sayer GL, Smith PD (2004) Immunocytochemical characterisation of the inflammatory cell infiltrate of varicose veins. Eur J Vasc Endovasc Surg 28:479–483CrossRefPubMedGoogle Scholar
  362. Schafer-Somi S, Ali Aksoy O, Patzl M, Findik M, Erunal-Maral N, Beceriklisoy HB, Polat B, Aslan S (2005) The activity of matrix metalloproteinase-2 and -9 in serum of pregnant and non-pregnant bitches. Reprod Domest Anim 40:46–50CrossRefPubMedGoogle Scholar
  363. Seah CC, Phillips TJ, Howard CE, Panova IP, Hayes CM, Asandra AS, Park HY (2005) Chronic wound fluid suppresses proliferation of dermal fibroblasts through a Ras-mediated signaling pathway. J Invest Dermatol 124:466–474CrossRefPubMedGoogle Scholar
  364. Sesso R, Franco MC (2010) Abnormalities in metalloproteinase pathways and IGF-I axis: a link between birth weight, hypertension, and vascular damage in childhood. Am J Hypertens 23:6–11CrossRefPubMedGoogle Scholar
  365. Shalinsky DR, Brekken J, Zou H, McDermott CD, Forsyth P, Edwards D, Margosiak S, Bender S, Truitt G, Wood A, Varki NM, Appelt K (1999) Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann N Y Acad Sci 878:236–270CrossRefPubMedGoogle Scholar
  366. Shi ZD, Ji XY, Berardi DE, Qazi H, Tarbell JM (2010) Interstitial flow induces MMP-1 expression and vascular SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism. Am J Physiol Heart Circ Physiol 298:H127–H135CrossRefPubMedGoogle Scholar
  367. Shimizu C, Matsubara T, Onouchi Y, Jain S, Sun S, Nievergelt CM, Shike H, Brophy VH, Takegawa T, Furukawa S, Akagi T, Newburger JW, Baker AL, Burgner D, Hibberd ML, Davila S, Levin M, Mamtani M, He W, Ahuja SK, Burns JC (2010) Matrix metalloproteinase haplotypes associated with coronary artery aneurysm formation in patients with Kawasaki disease. J Hum Genet 55:779–784CrossRefPubMedGoogle Scholar
  368. Shipley JM, Wesselschmidt RL, Kobayashi DK, Ley TJ, Shapiro SD (1996) Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci USA 93:3942–3946CrossRefPubMedGoogle Scholar
  369. Shokry M, Omran OM, Hassan HI, Elsedfy GO, Hussein MR (2009) Expression of matrix metalloproteinases 2 and 9 in human trophoblasts of normal and preeclamptic placentas: preliminary findings. Exp Mol Pathol 87:219–225CrossRefPubMedGoogle Scholar
  370. Silence J, Lupu F, Collen D, Lijnen HR (2001) Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol 21:1440–1445CrossRefPubMedGoogle Scholar
  371. Silence J, Collen D, Lijnen HR (2002) Reduced atherosclerotic plaque but enhanced aneurysm formation in mice with inactivation of the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene. Circ Res 90:897–903CrossRefPubMedGoogle Scholar
  372. Sinha I, Bethi S, Cronin P, Williams DM, Roelofs K, Ailawadi G, Henke PK, Eagleton MJ, Deeb GM, Patel HJ, Berguer R, Stanley JC, Upchurch GR Jr (2006) A biologic basis for asymmetric growth in descending thoracic aortic aneurysms: a role for matrix metalloproteinase 9 and 2. J Vasc Surg 43:342–348CrossRefPubMedGoogle Scholar
  373. Skiles JW, Gonnella NC, Jeng AY (2001) The design, structure, and therapeutic application of matrix metalloproteinase inhibitors. Curr Med Chem 8:425–474PubMedGoogle Scholar
  374. Skoog T, Ahokas K, Orsmark C, Jeskanen L, Isaka K, Saarialho-Kere U (2006) MMP-21 is expressed by macrophages and fibroblasts in vivo and in culture. Exp Dermatol 15:775–783CrossRefPubMedGoogle Scholar
  375. Slater SC, Koutsouki E, Jackson CL, Bush RC, Angelini GD, Newby AC, George SJ (2004) R-cadherin:beta-catenin complex and its association with vascular smooth muscle cell proliferation. Arterioscler Thromb Vasc Biol 24:1204–1210CrossRefPubMedGoogle Scholar
  376. Somerville RP, Oblander SA, Apte SS (2003) Matrix metalloproteinases: old dogs with new tricks. Genome Biol 4:216CrossRefPubMedGoogle Scholar
  377. Stefanidakis M, Koivunen E (2006) Cell-surface association between matrix metalloproteinases and integrins: role of the complexes in leukocyte migration and cancer progression. Blood 108:1441–1450CrossRefPubMedGoogle Scholar
  378. Steinhusen U, Weiske J, Badock V, Tauber R, Bommert K, Huber O (2001) Cleavage and shedding of E-cadherin after induction of apoptosis. J Biol Chem 276:4972–4980CrossRefPubMedGoogle Scholar
  379. Stoneman VE, Bennett MR (2004) Role of apoptosis in atherosclerosis and its therapeutic implications. Clin Sci (Lond) 107:343–354CrossRefGoogle Scholar
  380. Stracke JO, Fosang AJ, Last K, Mercuri FA, Pendas AM, Llano E, Perris R, Di Cesare PE, Murphy G, Knauper V (2000) Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP). FEBS Lett 478:52–56CrossRefPubMedGoogle Scholar
  381. Strickland DK, Ashcom JD, Williams S, Burgess WH, Migliorini M, Argraves WS (1990) Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor. J Biol Chem 265:17401–17404PubMedGoogle Scholar
  382. Subramaniam R, Haldar MK, Tobwala S, Ganguly B, Srivastava DK, Mallik S (2008) Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors. Bioorg Med Chem Lett 18:3333–3337CrossRefPubMedGoogle Scholar
  383. Suenaga N, Mori H, Itoh Y, Seiki M (2005) CD44 binding through the hemopexin-like domain is critical for its shedding by membrane-type 1 matrix metalloproteinase. Oncogene 24:859–868CrossRefPubMedGoogle Scholar
  384. Suzuki K, Enghild JJ, Morodomi T, Salvesen G, Nagase H (1990) Mechanisms of activation of tissue procollagenase by matrix metalloproteinase 3 (stromelysin). Biochemistry 29:10261–10270CrossRefPubMedGoogle Scholar
  385. Suzuki M, Raab G, Moses MA, Fernandez CA, Klagsbrun M (1997) Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site. J Biol Chem 272:31730–31737CrossRefPubMedGoogle Scholar
  386. Takase S, Bergan JJ, Schmid-Schonbein G (2000) Expression of adhesion molecules and cytokines on saphenous veins in chronic venous insufficiency. Ann Vasc Surg 14:427–435CrossRefPubMedGoogle Scholar
  387. Tan J, Hua Q, Xing X, Wen J, Liu R, Yang Z (2007) Impact of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 system on large arterial stiffness in patients with essential hypertension. Hypertens Res 30:959–963CrossRefPubMedGoogle Scholar
  388. Tarin C, Gomez M, Calvo E, Lopez JA, Zaragoza C (2009) Endothelial nitric oxide deficiency reduces MMP-13-mediated cleavage of ICAM-1 in vascular endothelium: a role in atherosclerosis. Arterioscler Thromb Vasc Biol 29:27–32CrossRefPubMedGoogle Scholar
  389. Tayebjee MH, Karalis I, Nadar SK, Beevers DG, MacFadyen RJ, Lip GY (2005) Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension. Am J Hypertens 18:325–329CrossRefPubMedGoogle Scholar
  390. Terashima M, Akita H, Kanazawa K, Inoue N, Yamada S, Ito K, Matsuda Y, Takai E, Iwai C, Kurogane H, Yoshida Y, Yokoyama M (1999) Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction. Circulation 99:2717–2719PubMedGoogle Scholar
  391. Teti A (1992) Regulation of cellular functions by extracellular matrix. J Am Soc Nephrol 2:S83–S87PubMedGoogle Scholar
  392. Thanabalasundaram G, Pieper C, Lischper M, Galla HJ (2010) Regulation of the blood-brain barrier integrity by pericytes via matrix metalloproteinases mediated activation of vascular endothelial growth factor in vitro. Brain Res 1347:1–10CrossRefPubMedGoogle Scholar
  393. Thompson AR, Drenos F, Hafez H, Humphries SE (2008) Candidate gene association studies in abdominal aortic aneurysm disease: a review and meta-analysis. Eur J Vasc Endovasc Surg 35:19–30CrossRefPubMedGoogle Scholar
  394. Toth M, Bernardo MM, Gervasi DC, Soloway PD, Wang Z, Bigg HF, Overall CM, DeClerck YA, Tschesche H, Cher ML, Brown S, Mobashery S, Fridman R (2000) Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (Membrane type 1)-MMP-dependent activation of pro-MMP-2. J Biol Chem 275:41415–41423CrossRefPubMedGoogle Scholar
  395. Tsai JH, Hwang JM, Ying TH, Shyu JC, Tsai CC, Hsieh YS, Wang YW, Liu JY, Kao SH (2009) The activation of matrix metalloproteinase-2 induced by protein kinase C alpha in decidualization. J Cell Biochem 108:547–554CrossRefPubMedGoogle Scholar
  396. Uglow EB, Slater S, Sala-Newby GB, Aguilera-Garcia CM, Angelini GD, Newby AC, George SJ (2003) Dismantling of cadherin-mediated cell-cell contacts modulates smooth muscle cell proliferation. Circ Res 92:1314–1321CrossRefPubMedGoogle Scholar
  397. Ulrich D, Lichtenegger F, Unglaub F, Smeets R, Pallua N (2005) Effect of chronic wound exudates and MMP-2/-9 inhibitor on angiogenesis in vitro. Plast Reconstr Surg 116:539–545CrossRefPubMedGoogle Scholar
  398. Uzui H, Harpf A, Liu M, Doherty TM, Shukla A, Chai NN, Tripathi PV, Jovinge S, Wilkin DJ, Asotra K, Shah PK, Rajavashisth TB (2002) Increased expression of membrane type 3-matrix metalloproteinase in human atherosclerotic plaque: role of activated macrophages and inflammatory cytokines. Circulation 106:3024–3030CrossRefPubMedGoogle Scholar
  399. Vaalamo M, Mattila L, Johansson N, Kariniemi AL, Karjalainen-Lindsberg ML, Kahari VM, Saarialho-Kere U (1997) Distinct populations of stromal cells express collagenase-3 (MMP-13) and collagenase-1 (MMP-1) in chronic ulcers but not in normally healing wounds. J Invest Dermatol 109:96–101CrossRefPubMedGoogle Scholar
  400. Valentin F, Bueb JL, Kieffer P, Tschirhart E, Atkinson J (2005) Oxidative stress activates MMP-2 in cultured human coronary smooth muscle cells. Fundam Clin Pharmacol 19:661–667CrossRefPubMedGoogle Scholar
  401. van de Ven WJ, Voorberg J, Fontijn R, Pannekoek H, van den Ouweland AM, van Duijnhoven HL, Roebroek AJ, Siezen RJ (1990) Furin is a subtilisin-like proprotein processing enzyme in higher eukaryotes. Mol Biol Rep 14:265–275CrossRefPubMedGoogle Scholar
  402. van der Laan WH, Quax PH, Seemayer CA, Huisman LG, Pieterman EJ, Grimbergen JM, Verheijen JH, Breedveld FC, Gay RE, Gay S, Huizinga TW, Pap T (2003) Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3. Gene Ther 10:234–242CrossRefPubMedGoogle Scholar
  403. van Laake LW, Vainas T, Dammers R, Kitslaar PJ, Hoeks AP, Schurink GW (2005) Systemic dilation diathesis in patients with abdominal aortic aneurysms: a role for matrix metalloproteinase-9? Eur J Vasc Endovasc Surg 29:371–377PubMedGoogle Scholar
  404. Van Lint P, Wielockx B, Puimege L, Noel A, Lopez-Otin C, Libert C (2005) Resistance of collagenase-2 (matrix metalloproteinase-8)-deficient mice to TNF-induced lethal hepatitis. J Immunol 175:7642–7649PubMedGoogle Scholar
  405. Van Wart HE, Birkedal-Hansen H (1990) The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci USA 87:5578–5582CrossRefPubMedGoogle Scholar
  406. Velasco G, Pendas AM, Fueyo A, Knauper V, Murphy G, Lopez-Otin C (1999) Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. J Biol Chem 274:4570–4576CrossRefPubMedGoogle Scholar
  407. Venturi M, Bonavina L, Annoni F, Colombo L, Butera C, Peracchia A, Mussini E (1996) Biochemical assay of collagen and elastin in the normal and varicose vein wall. J Surg Res 60:245–248CrossRefPubMedGoogle Scholar
  408. Vigetti D, Moretto P, Viola M, Genasetti A, Rizzi M, Karousou E, Clerici M, Bartolini B, Pallotti F, De Luca G, Passi A (2008) Aortic smooth muscle cells migration and the role of metalloproteinases and hyaluronan. Connect Tissue Res 49:189–192CrossRefPubMedGoogle Scholar
  409. Vihinen P, Ala-aho R, Kahari VM (2005) Matrix metalloproteinases as therapeutic targets in cancer. Curr Cancer Drug Targets 5:203–220CrossRefPubMedGoogle Scholar
  410. Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839CrossRefPubMedGoogle Scholar
  411. Voils SA, Evans ME, Lane MT, Schosser RH, Rapp RP (2005) Use of macrolides and tetracyclines for chronic inflammatory diseases. Ann Pharmacother 39:86–94PubMedGoogle Scholar
  412. von Steinburg SP, Kruger A, Fischer T, Mario Schneider KT, Schmitt M (2009) Placental expression of proteases and their inhibitors in patients with HELLP syndrome. Biol Chem 390:1199–1204CrossRefGoogle Scholar
  413. Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14:2123–2133CrossRefPubMedGoogle Scholar
  414. Waitkus-Edwards KR, Martinez-Lemus LA, Wu X, Trzeciakowski JP, Davis MJ, Davis GE, Meininger GA (2002) alpha(4)beta(1) Integrin activation of L-type calcium channels in vascular smooth muscle causes arteriole vasoconstriction. Circ Res 90:473–480CrossRefPubMedGoogle Scholar
  415. Wakisaka Y, Chu Y, Miller JD, Rosenberg GA, Heistad DD (2010) Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice. J Cereb Blood Flow Metab 30:56–69CrossRefPubMedGoogle Scholar
  416. Walker HA, Whitelock JM, Garl PJ, Nemenoff RA, Stenmark KR, Weiser-Evans MC (2003) Perlecan up-regulation of FRNK suppresses smooth muscle cell proliferation via inhibition of FAK signaling. Mol Biol Cell 14:1941–1952CrossRefPubMedGoogle Scholar
  417. Wall SJ, Sampson MJ, Levell N, Murphy G (2003) Elevated matrix metalloproteinase-2 and -3 production from human diabetic dermal fibroblasts. Br J Dermatol 149:13–16CrossRefPubMedGoogle Scholar
  418. Wang Z, Juttermann R, Soloway PD (2000) TIMP-2 is required for efficient activation of proMMP-2 in vivo. J Biol Chem 275:26411–26415CrossRefPubMedGoogle Scholar
  419. Wang X, Chow FL, Oka T, Hao L, Lopez-Campistrous A, Kelly S, Cooper S, Odenbach J, Finegan BA, Schulz R, Kassiri Z, Lopaschuk GD, Fernandez-Patron C (2009) Matrix metalloproteinase-7 and ADAM-12 (a disintegrin and metalloproteinase-12) define a signaling axis in agonist-induced hypertension and cardiac hypertrophy. Circulation 119:2480–2489CrossRefPubMedGoogle Scholar
  420. Weckroth M, Vaheri A, Lauharanta J, Sorsa T, Konttinen YT (1996) Matrix metalloproteinases, gelatinase and collagenase, in chronic leg ulcers. J Invest Dermatol 106:1119–1124CrossRefPubMedGoogle Scholar
  421. Whitlock GA, Dack KN, Dickinson RP, Lewis ML (2007) A novel series of highly selective inhibitors of MMP-3. Bioorg Med Chem Lett 17:6750–6753CrossRefPubMedGoogle Scholar
  422. Williamson RA, Marston FA, Angal S, Koklitis P, Panico M, Morris HR, Carne AF, Smith BJ, Harris TJ, Freedman RB (1990) Disulphide bond assignment in human tissue inhibitor of metalloproteinases (TIMP). Biochem J 268:267–274PubMedGoogle Scholar
  423. Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC (1999) Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113–117CrossRefPubMedGoogle Scholar
  424. Wilson WR, Schwalbe EC, Jones JL, Bell PR, Thompson MM (2005) Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm. Br J Surg 92:828–833CrossRefPubMedGoogle Scholar
  425. Wilson WR, Anderton M, Schwalbe EC, Jones JL, Furness PN, Bell PR, Thompson MM (2006) Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture. Circulation 113:438–445CrossRefPubMedGoogle Scholar
  426. Wilson WR, Anderton M, Choke EC, Dawson J, Loftus IM, Thompson MM (2008a) Elevated plasma MMP1 and MMP9 are associated with abdominal aortic aneurysm rupture. Eur J Vasc Endovasc Surg 35:580–584CrossRefPubMedGoogle Scholar
  427. Wilson WR, Choke EC, Dawson J, Loftus IM, Thompson MM (2008b) Plasma matrix metalloproteinase levels do not predict tissue levels in abdominal aortic aneurysms suitable for elective repair. Vascular 16:248–252CrossRefPubMedGoogle Scholar
  428. Woodside KJ, Hu M, Burke A, Murakami M, Pounds LL, Killewich LA, Daller JA, Hunter GC (2003) Morphologic characteristics of varicose veins: possible role of metalloproteinases. J Vasc Surg 38:162–169CrossRefPubMedGoogle Scholar
  429. Xiong W, Knispel RA, Dietz HC, Ramirez F, Baxter BT (2008) Doxycycline delays aneurysm rupture in a mouse model of Marfan syndrome. J Vasc Surg 47:166–172, discussion 172CrossRefPubMedGoogle Scholar
  430. Yan YL, Cohen SM (2007) Efficient synthesis of 5-amido-3-hydroxy-4-pyrones as inhibitors of matrix metalloproteinases. Org Lett 9:2517–2520CrossRefPubMedGoogle Scholar
  431. Ye S, Watts GF, Mandalia S, Humphries SE, Henney AM (1995) Preliminary report: genetic variation in the human stromelysin promoter is associated with progression of coronary atherosclerosis. Br Heart J 73:209–215CrossRefPubMedGoogle Scholar
  432. Yu YM, Lin HC (2010) Curcumin prevents human aortic smooth muscle cells migration by inhibiting of MMP-9 expression. Nutr Metab Cardiovasc Dis 20:125–132CrossRefPubMedGoogle Scholar
  433. Zamboni P, Scapoli G, Lanzara V, Izzo M, Fortini P, Legnaro R, Palazzo A, Tognazzo S, Gemmati D (2005) Serum iron and matrix metalloproteinase-9 variations in limbs affected by chronic venous disease and venous leg ulcers. Dermatol Surg 31:644–649, discussion 649CrossRefPubMedGoogle Scholar
  434. Zempo N, Koyama N, Kenagy RD, Lea HJ, Clowes AW (1996) Regulation of vascular smooth muscle cell migration and proliferation in vitro and in injured rat arteries by a synthetic matrix metalloproteinase inhibitor. Arterioscler Thromb Vasc Biol 16:28–33CrossRefPubMedGoogle Scholar
  435. Zervoudaki A, Economou E, Stefanadis C, Pitsavos C, Tsioufis K, Aggeli C, Vasiliadou K, Toutouza M, Toutouzas P (2003) Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment. J Hum Hypertens 17:119–124CrossRefPubMedGoogle Scholar
  436. Zhang YM, Fan X, Chakaravarty D, Xiang B, Scannevin RH, Huang Z, Ma J, Burke SL, Karnachi P, Rhodes KJ, Jackson PF (2008) 1-Hydroxy-2-pyridinone-based MMP inhibitors: synthesis and biological evaluation for the treatment of ischemic stroke. Bioorg Med Chem Lett 18:409–413CrossRefPubMedGoogle Scholar
  437. Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K, Takano Y (2006) Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res 26:3579–3583PubMedGoogle Scholar
  438. Zhou Z, Apte SS, Soininen R, Cao R, Baaklini GY, Rauser RW, Wang J, Cao Y, Tryggvason K (2000) Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci USA 97:4052–4057CrossRefPubMedGoogle Scholar
  439. Zhou Z, Shen T, Zhang BH, Lv XY, Lin HY, Zhu C, Xue LQ, Wang H (2009) The proprotein convertase furin in human trophoblast: possible role in promoting trophoblast cell migration and invasion. Placenta 30:929–938CrossRefPubMedGoogle Scholar
  440. Zureik M, Beaudeux JL, Courbon D, Benetos A, Ducimetiere P (2005) Serum tissue inhibitors of metalloproteinases 1 (TIMP-1) and carotid atherosclerosis and aortic arterial stiffness. J Hypertens 23:2263–2268CrossRefPubMedGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  1. 1.Vascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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