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Matrix Metalloproteinases and Hypertension

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Role of Proteases in Cellular Dysfunction

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 8))

Abstract

The matrix metalloproteinases (MMPs) are known for quite some time to play essential roles in this remodeling process of arteries found in hypertension, as will be discussed here. More recently, evidence indicates that some of them may not only influence hypertension due to their effect in remodeling but possibly by direct mechanisms such as the proteolytic change of vasoactive mediators. The most studied MMP in animal models of hypertension is MMP-2, and many such studies are described here. After a brief description of MMPs, we discuss data on MMPs in hypertension in three sections: findings on arteries, findings on the heart, and on the final section we then briefly discuss some other issues that may indicate that MMPs are related to hypertension in other yet unexplored ways. In this review we also highlight data showing the protective effects of MMP inhibition in arteries, heart, and kidney. MMP inhibition appears to be a relevant target for newer pharmacological intervention in hypertension. Doxycycline is the MMP inhibitor most widely used in cell cultures, animal studies on hypertension, and is a drug approved for commercial use for periodontal disease in the United States. The refinement of MMP assays and the specific delivery of different MMPs may highlight the specific role of each MMP in the different types of hypertension, enabling the use of a rational approach for a more specific inhibition of them in hypertension, so that target organs are more protected.

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References

  1. Lenfant C, Chobanian AV, Jones DW et al (2003) Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7): resetting the hypertension sails. Hypertension 41:1178-1179

    Article  PubMed  CAS  Google Scholar 

  2. Himmelmann A, Hedner T, Hansson L et al (1998) Isolated systolic hypertension: an important cardiovascular risk factor. Blood Press 7:197-207

    Article  PubMed  CAS  Google Scholar 

  3. Kannel WB (1993) Hypertension as a risk factor for cardiac events – epidemiologic results of long-term studies. J Cardiovasc Pharmacol 21 Suppl 2:S27-37

    Article  PubMed  Google Scholar 

  4. Zhang Y, Griendling KK, Dikalova A et al (2005) Vascular hypertrophy in angiotensin II-induced hypertension is mediated by vascular smooth muscle cell-derived H2O2. Hypertension 46:732-737

    Article  PubMed  CAS  Google Scholar 

  5. Griendling KK, FitzGerald GA (2003) Oxidative stress and cardiovascular injury: Part II: animal and human studies. Circulation 108:2034-2040

    Article  PubMed  Google Scholar 

  6. Ruddy JM, Jones JA, Stroud RE et al (2009) Differential effects of mechanical and biological stimuli on matrix metalloproteinase promoter activation in the thoracic aorta. Circulation 120:S262-268

    Article  PubMed  CAS  Google Scholar 

  7. Rizzi E, Castro MM, Prado CM et al (2010) Matrix metalloproteinase inhibition improves cardiac dysfunction and remodeling in 2-kidney, 1-clip hypertension. J Card Fail 16:599-608

    Article  PubMed  CAS  Google Scholar 

  8. Intengan HD, Schiffrin EL (2001) Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension 38:581-587

    Article  PubMed  CAS  Google Scholar 

  9. Duprez DA (2006) Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review. J Hypertens 24:983-991

    Article  PubMed  CAS  Google Scholar 

  10. Arribas SM, Hinek A, Gonzalez MC (2006) Elastic fibres and vascular structure in hypertension. Pharmacol Ther 111:771-791

    Article  PubMed  CAS  Google Scholar 

  11. Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463-516

    Article  PubMed  CAS  Google Scholar 

  12. Nagase H, Woessner Jr F (1999) Matrix Metalloproteinases. The Journal of Biological Chemistry 274:21491-21494

    Article  PubMed  CAS  Google Scholar 

  13. 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 U S A 87:5578-5582

    Article  PubMed  Google Scholar 

  14. Woessner JF, Jr (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145-2154

    PubMed  CAS  Google Scholar 

  15. Kandasamy AD, Chow AK, Ali MA et al (2010) Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix. Cardiovasc Res 85:413-423

    Article  PubMed  CAS  Google Scholar 

  16. Viappiani S, Nicolescu AC, Holt A et al (2009) Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione. Biochem Pharmacol 77:826-834

    Article  PubMed  CAS  Google Scholar 

  17. Okamoto T, Akaike T, Sawa T et al (2001) Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation. J Biol Chem 276:29596-29602

    Article  PubMed  CAS  Google Scholar 

  18. Gomez DE, Alonso DF, Yoshiji H et al (1997) Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74:111-122

    PubMed  CAS  Google Scholar 

  19. Raffetto JD, Khalil RA (2008) Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 75:346-359

    Article  PubMed  CAS  Google Scholar 

  20. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8:221-233

    Article  PubMed  CAS  Google Scholar 

  21. Berk BC, Fujiwara K, Lehoux S (2007) ECM remodeling in hypertensive heart disease. J Clin Invest 117:568-575

    Article  PubMed  CAS  Google Scholar 

  22. Yasmin, McEniery CM, Wallace S et al (2005) Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness. Arterioscler Thromb Vasc Biol 25:372-378

    Google Scholar 

  23. Martinez ML, Lopes LF, Coelho EB et al (2006) Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension. J Cardiovasc Pharmacol 47:117-122

    Article  PubMed  CAS  Google Scholar 

  24. Zile MR, Desantis SM, Baicu CF et al (2011) Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure. Circ Heart Fail 4:246-256

    Article  PubMed  CAS  Google Scholar 

  25. Castro MM, Rizzi E, Figueiredo-Lopes L et al (2008) Metalloproteinase inhibition ameliorates hypertension and prevents vascular dysfunction and remodeling in renovascular hypertensive rats. Atherosclerosis 198:320-331

    Article  PubMed  CAS  Google Scholar 

  26. Castro MM, Rizzi E, Prado CM et al (2009) Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling. Matrix Biol 29:194-201

    Article  PubMed  Google Scholar 

  27. Bouvet C, Gilbert LA, Girardot D et al (2005) Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition. Hypertension 45:432-437

    Article  PubMed  CAS  Google Scholar 

  28. Flamant M, Placier S, Dubroca C et al (2007) Role of matrix metalloproteinases in early hypertensive vascular remodeling. Hypertension 50:212-218

    Article  PubMed  CAS  Google Scholar 

  29. Ahmed SH, Clark LL, Pennington WR et al (2006) Matrix metalloproteinases/tissue inhibitors of metalloproteinases: relationship between changes in proteolytic determinants of matrix composition and structural, functional, and clinical manifestations of hypertensive heart disease. Circulation 113:2089-2096

    Article  PubMed  CAS  Google Scholar 

  30. Spinale FG (2007) Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 87:1285-1342

    Article  PubMed  CAS  Google Scholar 

  31. Galis ZS, Khatri JJ (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 90:251-262

    PubMed  CAS  Google Scholar 

  32. Newby AC (2006) Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates. Cardiovasc Res 69:614-624

    Article  PubMed  CAS  Google Scholar 

  33. Castro MM, Kandasamy AD, Youssef N et al (2011) Matrix metalloproteinase inhibitor properties of tetracyclines: therapeutic potential in cardiovascular diseases. Pharmacol Res 64:551-560

    Article  PubMed  CAS  Google Scholar 

  34. Martinez-Lemus LA, Zhao G, Galinanes EL et al (2011) Inward remodeling of resistance arteries requires reactive oxygen species-dependent activation of matrix metalloproteinases. Am J Physiol Heart Circ Physiol 300:H2005-2015

    Article  PubMed  CAS  Google Scholar 

  35. Lemarie CA, Tharaux PL, Lehoux S (2009) Extracellular matrix alterations in hypertensive vascular remodeling. J Mol Cell Cardiol 48:433-439

    Article  PubMed  Google Scholar 

  36. Ceron CS, Rizzi E, Guimaraes DA et al (2012) Time course involvement of matrix metalloproteinases in the vascular alterations of renovascular hypertension. Matrix Biol 31:261-270

    Article  PubMed  CAS  Google Scholar 

  37. Intengan HD, Schiffrin EL (2000) Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension 36:312-318

    Article  PubMed  CAS  Google Scholar 

  38. Martins-Oliveira A, Castro MM, Oliveira DM et al (2013) Contrasting effects of aliskiren versus losartan on hypertensive vascular remodeling. Int J Cardiol 167(4):1199-1205

    Google Scholar 

  39. 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 24:54-60

    Article  PubMed  CAS  Google Scholar 

  40. Zempo N, Koyama N, Kenagy RD et al (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 16:28-33

    Article  PubMed  CAS  Google Scholar 

  41. Bendeck MP, Conte M, Zhang M et al (2002) Doxycycline modulates smooth muscle cell growth, migration, and matrix remodeling after arterial injury. Am J Pathol 160:1089-1095

    Article  PubMed  CAS  Google Scholar 

  42. 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 91:845-851

    Article  PubMed  CAS  Google Scholar 

  43. Chao JT, Davis MJ (2011) The roles of integrins in mediating the effects of mechanical force and growth factors on blood vessels in hypertension. Curr Hypertens Rep 13:421-429

    Article  PubMed  CAS  Google Scholar 

  44. Lehoux S, Castier Y, Tedgui A (2006) Molecular mechanisms of the vascular responses to haemodynamic forces. J Intern Med 259:381-392

    Article  PubMed  CAS  Google Scholar 

  45. Lehoux S, Tedgui A (1998) Signal transduction of mechanical stresses in the vascular wall. Hypertension 32:338-345

    Article  PubMed  CAS  Google Scholar 

  46. Li Z, Froehlich J, Galis ZS et al (1999) Increased expression of matrix metalloproteinase-2 in the thickened intima of aged rats. Hypertension 33:116-123

    Article  PubMed  CAS  Google Scholar 

  47. Sartore S, Chiavegato A, Faggin E et al (2001) Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: from innocent bystander to active participant. Circ Res 89:1111-1121

    Article  PubMed  CAS  Google Scholar 

  48. Filippov S, Koenig GC, Chun TH et al (2005) MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells. J Exp Med 202:663-671

    Article  PubMed  CAS  Google Scholar 

  49. Watts SW, Rondelli C, Thakali K et al (2007) Morphological and biochemical characterization of remodeling in aorta and vena cava of DOCA-salt hypertensive rats. Am J Physiol Heart Circ Physiol 292:H2438-2448

    Article  PubMed  CAS  Google Scholar 

  50. Rizzoni D, Muiesan ML, Porteri E et al (2009) Vascular remodeling, macro- and microvessels: therapeutic implications. Blood Press 18:242-246

    PubMed  Google Scholar 

  51. Greenwald SE (2007) Ageing of the conduit arteries. J Pathol 211:157-172

    Article  PubMed  CAS  Google Scholar 

  52. Zieman SJ, Melenovsky V, Kass DA (2005) Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 25:932-943

    Article  PubMed  CAS  Google Scholar 

  53. Qin X, Corriere MA, Matrisian LM et al (2006) Matrix metalloproteinase inhibition attenuates aortic calcification. Arterioscler Thromb Vasc Biol 26:1510-1516

    Article  PubMed  CAS  Google Scholar 

  54. Briones AM, Arribas SM, Salaices M (2010) Role of extracellular matrix in vascular remodeling of hypertension. Curr Opin Nephrol Hypertens 19:187-194

    Article  PubMed  CAS  Google Scholar 

  55. Bouvet C, Moreau S, Blanchette J et al (2008) Sequential activation of matrix metalloproteinase 9 and transforming growth factor beta in arterial elastocalcinosis. Arterioscler Thromb Vasc Biol 28:856-862

    Article  PubMed  CAS  Google Scholar 

  56. Guimaraes DA, Rizzi E, Ceron CS et al (2011) Doxycycline dose-dependently inhibits MMP-2-mediated vascular changes in 2K1C hypertension. Basic Clin Pharmacol Toxicol 108:318-325

    Article  PubMed  CAS  Google Scholar 

  57. Nagareddy P, Rajput P, Vasudevan H et al (2012) Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin resistant rats. Br J Pharmacol 165(3):705-715

    Google Scholar 

  58. Zeydanli EN, Kandilci HB, Turan B (2011) Doxycycline ameliorates vascular endothelial and contractile dysfunction in the thoracic aorta of diabetic rats. Cardiovasc Toxicol 11:134-147

    Article  PubMed  CAS  Google Scholar 

  59. Su J, Palen DI, Lucchesi PA et al (2006) Mice lacking the gene encoding for MMP-9 and resistance artery reactivity. Biochem Biophys Res Commun 349:1177-1181

    Article  PubMed  CAS  Google Scholar 

  60. Rodrigues SF, Tran ED, Fortes ZB et al (2010) Matrix metalloproteinases cleave the beta2-adrenergic receptor in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 299:H25-35

    Article  PubMed  CAS  Google Scholar 

  61. Hao L, Du M, Lopez-Campistrous A et al (2004) Agonist-induced activation of matrix metalloproteinase-7 promotes vasoconstriction through the epidermal growth factor-receptor pathway. Circ Res 94:68-76

    Article  PubMed  CAS  Google Scholar 

  62. Hao L, Nishimura T, Wo H et al (2006) Vascular responses to alpha1-adrenergic receptors in small rat mesenteric arteries depend on mitochondrial reactive oxygen species. Arterioscler Thromb Vasc Biol 26:819-825

    Article  PubMed  CAS  Google Scholar 

  63. Wu KI, Schmid-Schonbein GW (2011) Nuclear factor kappa B and matrix metalloproteinase induced receptor cleavage in the spontaneously hypertensive rat. Hypertension 57:261-268

    Article  PubMed  CAS  Google Scholar 

  64. Fernandez-Patron C, Radomski MW, Davidge ST (1999) Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res 85:906-911

    Article  PubMed  CAS  Google Scholar 

  65. Abdalvand A, Morton JS, Bourque SL et al (2013) Matrix metalloproteinase enhances big-endothelin-1 constriction in mesenteric vessels of pregnant rats with reduced uterine blood flow. Hypertension 61:488-493

    Article  PubMed  CAS  Google Scholar 

  66. Fernandez-Patron C, Stewart KG, Zhang Y et al (2000) Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Circ Res 87:670-676

    Article  PubMed  CAS  Google Scholar 

  67. Martinez A, Oh HR, Unsworth EJ et al (2004) Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator. Biochem J 383:413-418

    Article  PubMed  CAS  Google Scholar 

  68. Rizzi E, Ceron CS, Guimaraes DA et al (2012) Temporal changes in cardiac matrix metalloproteinase activity, oxidative stress, and TGF-beta in renovascular hypertension-induced cardiac hypertrophy. Exp Mol Pathol 94:1-9

    Article  PubMed  Google Scholar 

  69. Rizzi E, Castro MM, Ceron CS et al (2013) Tempol inhibits TGF-beta and MMPs upregulation and prevents cardiac hypertensive changes. Int J Cardiol 165(1):165-173. doi:10.1016/j.ijcard.2011.08.060

    Google Scholar 

  70. Bergman MR, Teerlink JR, Mahimkar R et al (2007) Cardiac matrix metalloproteinase-2 expression independently induces marked ventricular remodeling and systolic dysfunction. Am J Physiol Heart Circ Physiol 292:H1847-1860

    Article  PubMed  CAS  Google Scholar 

  71. Mahimkar R, Nguyen A, Mann M et al (2009) Cardiac transgenic matrix metalloproteinase-2 expression induces myxomatous valve degeneration: a potential model of mitral valve prolapse disease. Cardiovasc Pathol 18:253-261

    Article  PubMed  CAS  Google Scholar 

  72. Matsusaka H, Ide T, Matsushima S et al (2006) Targeted deletion of matrix metalloproteinase 2 ameliorates myocardial remodeling in mice with chronic pressure overload. Hypertension 47:711-717

    Article  PubMed  CAS  Google Scholar 

  73. Zhou HZ, Ma X, Gray MO et al (2007) Transgenic MMP-2 expression induces latent cardiac mitochondrial dysfunction. Biochem Biophys Res Commun 358:189-195

    Article  PubMed  CAS  Google Scholar 

  74. Wang W, Schulze CJ, Suarez-Pinzon WL et al (2002) Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury. Circulation 106:1543-1549

    Article  PubMed  CAS  Google Scholar 

  75. Sawicki G, Leon H, Sawicka J et al (2005) Degradation of myosin light chain in isolated rat hearts subjected to ischemia-reperfusion injury: a new intracellular target for matrix metalloproteinase-2. Circulation 112:544-552

    Article  PubMed  CAS  Google Scholar 

  76. Sung MM, Schulz CG, Wang W et al (2007) Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. J Mol Cell Cardiol 43:429-436

    Article  PubMed  CAS  Google Scholar 

  77. Ali MAM, Cho WJ, Hudson B et al (2010) Titin is a Target of Matrix Metalloproteinase-2 Implications in Myocardial Ischemia/Reperfusion Injury. Circulation 122:2039-U2106

    Article  PubMed  CAS  Google Scholar 

  78. Cheung PY, Sawicki G, Wozniak M et al (2000) Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation 101:1833-1839

    Article  PubMed  CAS  Google Scholar 

  79. Kwan JA, Schulze CJ, Wang WJ et al (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 Journal 18:690

    Google Scholar 

  80. Lovett DH, Mahimkar R, Raffai RL et al (2012) A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity. PLoS ONE 7:e34177

    Article  PubMed  CAS  Google Scholar 

  81. Romanic AM, Harrison SM, Bao W et al (2002) Myocardial protection from ischemia/reperfusion injury by targeted deletion of matrix metalloproteinase-9. Cardiovasc Res 54:549-558

    Article  PubMed  CAS  Google Scholar 

  82. Odenbach J, Wang X, Cooper S et al (2011) MMP-2 mediates angiotensin II-induced hypertension under the transcriptional control of MMP-7 and TACE. Hypertension 57:123-130

    Article  PubMed  CAS  Google Scholar 

  83. Zhou S, Feely J, Spiers JP et al (2007) Matrix metalloproteinase-9 polymorphism contributes to blood pressure and arterial stiffness in essential hypertension. J Hum Hypertens 21:861-867

    Article  PubMed  CAS  Google Scholar 

  84. Li-Saw-Hee FL, Edmunds E, Blann AD et al (2000) Matrix metalloproteinase-9 and tissue inhibitor metalloproteinase-1 levels in essential hypertension. Relationship to left ventricular mass and anti-hypertensive therapy. Int J Cardiol 75:43-47

    Article  PubMed  CAS  Google Scholar 

  85. Zervoudaki A, Economou E, Pitsavos C et al (2004) The effect of Ca2+ channel antagonists on plasma concentrations of matrix metalloproteinase-2 and -9 in essential hypertension. Am J Hypertens 17:273-276

    Google Scholar 

  86. Friese RS, Rao F, Khandrika S et al (2009) Matrix metalloproteinases: discrete elevations in essential hypertension and hypertensive end-stage renal disease. Clin Exp Hypertens 31:521-533

    Article  PubMed  CAS  Google Scholar 

  87. Cheng S, Lovett DH (2003) Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol 162:1937-1949

    Article  PubMed  CAS  Google Scholar 

  88. Cheng S, Pollock AS, Mahimkar R et al (2006) Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury. FASEB J 20:1898-1900

    Article  PubMed  CAS  Google Scholar 

  89. Williams JM, Zhang J, North P et al (2011) Evaluation of metalloprotease inhibitors on hypertension and diabetic nephropathy. Am J Physiol Renal Physiol 300:F983-998

    Article  PubMed  CAS  Google Scholar 

  90. Boos CJ, Lip GY (2006) Is hypertension an inflammatory process? Curr Pharm Des 12:1623-1635

    Article  PubMed  CAS  Google Scholar 

  91. Singh T, Newman AB (2011) Inflammatory markers in population studies of aging. Ageing Res Rev 10:319-329

    Article  PubMed  CAS  Google Scholar 

  92. Blankenberg S, Rupprecht HJ, Poirier O et al (2003) Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 107:1579–1585

    Article  PubMed  CAS  Google Scholar 

  93. Cimmino G, Ragni M, Cirillo P et al (2013) C-reactive protein induces expression of matrix metalloproteinase-9: a possible link between inflammation and plaque rupture. Int J Cardiol 168(2):981-986. doi:10.1016/j.ijcard.2012.10.040

    Google Scholar 

  94. Albandar JM, Brunelle JA, Kingman A (1999) Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol 70:13-29

    Article  PubMed  CAS  Google Scholar 

  95. Demmer RT, Desvarieux M (2006) Periodontal infections and cardiovascular disease: the heart of the matter. J Am Dent Assoc 137 Suppl:14S-20S; quiz 38S

    Google Scholar 

  96. Loos BG (2006) Systemic effects of periodontitis. Int J Dent Hyg 4 Suppl 1:34-38; discussion 50-32

    Article  PubMed  Google Scholar 

  97. Paraskevas S, Huizinga JD, Loos BG (2008) A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol 35:277-290

    Article  PubMed  CAS  Google Scholar 

  98. Marcaccini AM, Novaes AB, Jr., Meschiari CA et al (2009) Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy. Clin Chim Acta 409:117-122

    Article  PubMed  CAS  Google Scholar 

  99. Tonetti MS, D'Aiuto F, Nibali L et al (2007) Treatment of periodontitis and endothelial function. N Engl J Med 356:911-920

    Article  PubMed  CAS  Google Scholar 

  100. Kai H, Ikeda H, Yasukawa H et al (1998) Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol 32:368-372

    Article  PubMed  CAS  Google Scholar 

  101. Wu TC, Leu HB, Lin WT et al (2005) Plasma matrix metalloproteinase-3 level is an independent prognostic factor in stable coronary artery disease. Eur J Clin Invest 35:537-545

    Article  PubMed  CAS  Google Scholar 

  102. Hadler-Olsen E, Winberg JO, Reinholt FP et al (2011) Proteases in Plasma and Kidney of db/db Mice as Markers of Diabetes-Induced Nephropathy. ISRN Endocrinol 2011:832642

    PubMed  CAS  Google Scholar 

  103. Zayani Y, Allal-Elasmi M, Jacob MP et al (2012) Abnormal circulating levels of matrix metalloproteinases and their inhibitors in diabetes mellitus. Clin Lab 58:779-785

    PubMed  CAS  Google Scholar 

  104. Novak MJ, Johns LP, Miller RC et al (2002) Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe, generalized, chronic periodontitis. J Periodontol 73:762-769

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, Brazil

    Alejandro F. Prado

  2. Department of Pharmacology, University of Alberta, Edmonton, AB, Canada

    Michele M. Castro

  3. Cardiovascular Research Centre, 4-62 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada

    Michele M. Castro

  4. Department of Morphology and Physiology, Dental School of Ribeirao Preto, University of São Paulo, Avenida do Café, S/N, Monte Alegre, CEP: 14040-904, Ribeirao Preto, SP, Brazil

    Raquel F. Gerlach

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  1. Alejandro F. Prado
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  2. Michele M. Castro
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  3. Raquel F. Gerlach
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Correspondence to Raquel F. Gerlach .

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  1. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

  2. Dept of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

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Prado, A.F., Castro, M.M., Gerlach, R.F. (2014). Matrix Metalloproteinases and Hypertension. In: Dhalla, N., Chakraborti, S. (eds) Role of Proteases in Cellular Dysfunction. Advances in Biochemistry in Health and Disease, vol 8. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9099-9_15

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