Cell and Tissue Research

, Volume 347, Issue 1, pp 155–175 | Cite as

Transforming growth factor-β and atherosclerosis: interwoven atherogenic and atheroprotective aspects

Review

Abstract

Age-related progression of cardiovascular disease is by far the largest health problem in the US and involves vascular damage, progressive vascular fibrosis and the accumulation of lipid-rich atherosclerotic lesions. Advanced lesions can restrict flow to key organs and can trigger occlusive thrombosis resulting in a stroke or myocardial infarction. Transforming growth factor-beta (TGF-β) is a major orchestrator of the fibroproliferative response to tissue damage. In the early stages of repair, TGF-β is released from platelets and activated from matrix reservoirs; it then stimulates the chemotaxis of repair cells, modulates immunity and inflammation and induces matrix production. At later stages, it negatively regulates fibrosis through its strong antiproliferative and apoptotic effects on fibrotic cells. In advanced lesions, TGF-β might be important in arterial calcification, commonly referred to as “hardening of the arteries”. Because TGF-β can signal through multiple pathways, namely the SMADs, a MAPK pathway and the Rho/ROCK pathways, selective defects in TGF-β signaling can disrupt otherwise coordinated pathways of tissue regeneration. TGF-β is known to control cell proliferation, cell migration, matrix synthesis, wound contraction, calcification and the immune response, all being major components of the atherosclerotic process. However, many of the effects of TGF-β are essential to normal tissue repair and thus, TGF-β is often thought to be “atheroprotective”. The present review attempts to parse systematically the known effects of TGF-β on both the major risk factors for atherosclerosis and to isolate the role of TGF-β in the many component pathways involved in atherogenesis.

Keywords

Transforming growth factor Atherosclerosis Cardiovascular disease Restenosis Gene expression 

References

  1. Abe R, Donnelly SC, Peng T, Bucala R, Metz CN (2001) Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 166:7556–7562PubMedGoogle Scholar
  2. Ahuja SS, Paliogianni F, Yamada H, Balow JE, Boumpas DT (1993) Effect of transforming growth factor-beta on early and late activation events in human T cells. J Immunol 150:3109–3118PubMedGoogle Scholar
  3. Akhurst RJ (2004) TGF[beta] signaling in health and disease. Nat Genet 36:790–792PubMedGoogle Scholar
  4. Alexandrow MG, Kawabata M, Aakre M, Moses HL (1995) Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor beta 1. Proc Natl Acad Sci USA 92:3239–3243PubMedGoogle Scholar
  5. Andres JL, Stanley K, Cheifetz S, Massague J (1989) Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-β. J Cell Biol 109:3137–3145PubMedGoogle Scholar
  6. Assoian RK, Sporn MB (1986) Type β transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol 102:1217–1223PubMedGoogle Scholar
  7. August P, Sharma V, Ding R, Schwartz JE, Suthanthiran M (2009) Transforming growth factor beta and excess burden of renal disease. Trans Am Clin Climatol Assoc 120:61–72PubMedGoogle Scholar
  8. Bachman KE, Blair BG, Brenner K, Bardelli A, Arena S, Zhou S, Hicks J, De Marzo AM, Argani P, Park BH (2004) p21(WAF1/CIP1) mediates the growth response to TGF-beta in human epithelial cells. Cancer Biol Ther 3:221–225PubMedGoogle Scholar
  9. Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross R (1990) TGF-β induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 63:515–524PubMedGoogle Scholar
  10. Belizna CC, Richard V, Primard E, Kerleau JM, Cailleux N, Louvel JP, Marie I, Hamidou M, Thuillez C, Levesque H (2008) Early atheroma in primary and secondary antiphospholipid syndrome: an intrinsic finding. Semin Arthritis Rheum 37:373–380PubMedGoogle Scholar
  11. Bell JA, Bell L (1989) Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells. Circ Res 65:1057–1065PubMedGoogle Scholar
  12. Bennett MR, Littlewood TD, Schwartz SM, Weissberg PL (1997) Increased sensitivity of human vascular smooth muscle cells from atherosclerotic plaques to p53-mediated apoptosis. Circ Res 81:591–599PubMedGoogle Scholar
  13. Bhowmick NA, Ghiassi M, Aakre M, Brown K, Singh V, Moses HL (2003) TGF-beta-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest. Proc Natl Acad Sci USA 100:15548–15553PubMedGoogle Scholar
  14. Bjorkerud S (1991) Effects of transforming growth factor-b1 on human arterial smooth muscle cells in vitro. Arteriosclerosis 11:892–902Google Scholar
  15. Bobik A (2006) Transforming growth factor-betas and vascular disorders. Arterioscler Thromb Vasc Biol 26:1712–1720PubMedGoogle Scholar
  16. Bobik A, Agrotis A, Kanellakis P, Dilley R, Krushinsky A, Smirnov V, Tararak E, Condron M, Kostolias G (1999) Distinct patterns of transforming growth factor-beta isoform and receptor expression in human atherosclerotic lesions. Colocalization implicates TGF-beta in fibrofatty lesion development. Circulation 99:2883–2891PubMedGoogle Scholar
  17. Bochaton-Piallat M-L, Gabbiani F, Ropraz P, Gabbiani G (1993) Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones. Arteriocler Thromb Vasc Biol 13:1449–1455Google Scholar
  18. Bochaton-Piallat ML, Gabbiani F, Redard M, Desmouliere A, Gabbiani G (1995) Apoptosis participates in cellularity regulation during rat aortic intimal thickening. Am J Pathol 146:1059–1064PubMedGoogle Scholar
  19. Bonecini-Almeida MG, Ho JL, Boechat N, Huard RC, Chitale S, Doo H, Geng J, Rego L, Lazzarini LC, Kritski AL, Johnson WD Jr, McCaffrey TA, Silva JR (2004) Down-modulation of lung immune responses by interleukin-10 and transforming growth factor beta (TGF-beta) and analysis of TGF-beta receptors I and II in active tuberculosis. Infect Immun 72:2628–2634PubMedGoogle Scholar
  20. Borrelli V, Marzo L di, Sapienza P, Colasanti M, Moroni E, Cavallaro A (2006) Role of platelet-derived growth factor and transforming growth factor beta1 in the regulation of metalloproteinase expressions. Surgery 140:454–463PubMedGoogle Scholar
  21. Boyd FT, Cheifetz S, Andres J, Laiho M, Massague J (1990) Transforming growth factor-b receptors and binding proteoglycans. J Cell Sci Suppl 13:131–138PubMedGoogle Scholar
  22. Bray PJ, Du B, Mejia VM, Hao SC, Deutsch E, Fu C, Wilson RC, Hanauske-Abel H, McCaffrey TA (1999) Glucocorticoid resistance caused by reduced expression of the glucocorticoid receptor in cells from human vascular lesions. Arterioscler Thromb Vasc Biol 19:1180–1189PubMedGoogle Scholar
  23. Brizzi MF, Dentelli P, Rosso A, Calvi C, Gambino R, Cassader M, Salvidio G, Deferrari G, Camussi G, Pegoraro L, Pagano G, Cavallo-Perin P (2004) RAGE- and TGF-beta receptor-mediated signals converge on STAT5 and p21waf to control cell-cycle progression of mesangial cells: a possible role in the development and progression of diabetic nephropathy. FASEB J 18:1249–1251PubMedGoogle Scholar
  24. Buday A, Orsy P, Godo M, Mozes M, Kokeny G, Lacza Z, Koller A, Ungvari Z, Gross ML, Benyo Z, Hamar P (2010) Elevated systemic TGF-beta impairs aortic vasomotor function through activation of NADPH oxidase-driven superoxide production and leads to hypertension, myocardial remodeling, and increased plaque formation in apoE(−/−) mice. Am J Physiol Heart Circ Physiol 299:H386–H395PubMedGoogle Scholar
  25. Buoro S, Ferrarese P, Chiavegato A, Roelofs M, Scatena M, Pauletto P, Passerini-Glazel G, Pagano F, Sartore S (1993) Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction. Lab Invest 69:589–602PubMedGoogle Scholar
  26. Burch ML, Ballinger ML, Yang SN, Getachew R, Itman C, Loveland K, Osman N, Little PJ (2010) Thrombin stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by protease-activated receptor-1 transactivation of the transforming growth factor beta type I receptor. J Biol Chem 285:26798–26805PubMedGoogle Scholar
  27. Chaouat A, Coulet F, Favre C, Simonneau G, Weitzenblum E, Soubrier F, Humbert M (2004) Endoglin germline mutation in a patient with hereditary haemorrhagic telangiectasia and dexfenfluramine associated pulmonary arterial hypertension. Thorax 59:446–448PubMedGoogle Scholar
  28. Chen CL, Liu IH, Fliesler SJ, Han X, Huang SS, Huang JS (2007) Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis. J Cell Sci 120:3509–3521PubMedGoogle Scholar
  29. Chen CL, Huang SS, Huang JS (2008) Cholesterol modulates cellular TGF-beta responsiveness by altering TGF-beta binding to TGF-beta receptors. J Cell Physiol 215:223–233PubMedGoogle Scholar
  30. Chen JK, Hoshi H, McKeehan WL (1987) Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc Natl Acad Sci USA 84:5287–5291PubMedGoogle Scholar
  31. Chen W, Chu Y, Zhu D, Yan C, Liu J, Ji K, Gao P (2009) Perivascular gene transfer of dominant-negative N19RhoA attenuates neointimal formation via inhibition of TGF-beta1-Smad2 signaling in rats after carotid artery balloon injury. Biochem Biophys Res Commun 389:217–223PubMedGoogle Scholar
  32. Cipollone F, Fazia M, Mincione G, Iezzi A, Pini B, Cuccurullo C, Ucchino S, Spigonardo F, Di Nisio M, Cuccurullo F, Mezzetti A, Porreca E (2004) Increased expression of transforming growth factor-beta1 as a stabilizing factor in human atherosclerotic plaques. Stroke 35:2253–2257PubMedGoogle Scholar
  33. Claassen GF, Hann SR (2000) A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta-induced cell-cycle arrest. Proc Natl Acad Sci USA 97:9498–9503PubMedGoogle Scholar
  34. Clark KJ, Cary NR, Grace AA, Metcalfe JC (2001) Microsatellite mutation of type II transforming growth factor-beta receptor is rare in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21:555–559PubMedGoogle Scholar
  35. Datto MB, Yu Y, Wang XF (1995) Functional analysis of the transforming growth factor beta responsive elements in the WAF1/Cip1/p21 promoter. J Biol Chem 270:28623–28628PubMedGoogle Scholar
  36. Ebner R, Chen RH, Shum L, Lawler S, Zioncheck TF, Lee A, Lopez AR, Derynck R (1993) Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor. Science 260:1344–1348PubMedGoogle Scholar
  37. Edlin RS, Tsai S, Yamanouchi D, Wang C, Liu B, Kent KC (2009) Characterization of primary and restenotic atherosclerotic plaque from the superficial femoral artery: potential role of Smad3 in regulation of SMC proliferation. J Vasc Surg 49:1289–1295PubMedGoogle Scholar
  38. Enos WF Jr, Beyer JC, Holmes RH (1955) Pathogenesis of coronary disease in American soldiers killed in Korea. J Am Med Assoc 158:912–914PubMedGoogle Scholar
  39. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293–298PubMedGoogle Scholar
  40. Evans RA, Tian YC, Steadman R, Phillips AO (2003) TGF-beta1-mediated fibroblast-myofibroblast terminal differentiation—the role of Smad proteins. Exp Cell Res 282:90–100PubMedGoogle Scholar
  41. Fadini GP, Tjwa M (2010) A role for TGF-beta in transforming endothelial progenitor cells into neointimal smooth muscle cells. Atherosclerosis 211:32–35PubMedGoogle Scholar
  42. Falcone DJ, McCaffrey TA, Haimovitz-Friedman A, Garcia M (1993a) Transforming growth factor-beta 1 stimulates macrophage urokinase expression and release of matrix-bound basic fibroblast growth factor. J Cell Physiol 155:595–605PubMedGoogle Scholar
  43. Falcone DJ, McCaffrey TA, Haimovitz-Friedman A, Vergilio JA, Nicholson AC (1993b) Macrophage and foam cell release of matrix-bound growth factors. Role of plasminogen activation. J Biol Chem 268:11951–11958PubMedGoogle Scholar
  44. Fassing CH, Yingling JM, Howe DJ, Wang T, He WW, Gustafson ML, Shah P, Donahoe PK, Wang XF (1994) A transforming growth factor b type I receptor that signals to activate gene expression. Science 263:87–89Google Scholar
  45. Feinberg MW, Jain MK (2005) Role of transforming growth factor-beta1/Smads in regulating vascular inflammation and atherogenesis. Panminerva Med 47:169–186PubMedGoogle Scholar
  46. Feinberg MW, Watanabe M, Lebedeva MA, Depina AS, Hanai J, Mammoto T, Frederick JP, Wang XF, Sukhatme VP, Jain MK (2004) Transforming growth factor-beta1 inhibition of vascular smooth muscle cell activation is mediated via Smad3. J Biol Chem 279:16388–16393PubMedGoogle Scholar
  47. Flanders KC, Thompson NL, Cissel DS, Van Obberghen-Schilling E, Baker CC, Kass ME, Ellingsworth LR, Roberts AB, Sporn MB (1989) Transforming growth factor-b1: histochemical localization with antibodies to different epitopes. J Cell Biol 108:653–660PubMedGoogle Scholar
  48. Fleenor BS, Marshall KD, Durrant JR, Lesniewski LA, Seals DR (2010) Arterial stiffening with ageing is associated with transforming growth factor-beta1-related changes in adventitial collagen: reversal by aerobic exercise. J Physiol (Lond) 588:3971–3982Google Scholar
  49. Franzen P, Dijke P, Ichijo H, Yamashita H, Schulz H, Heldin C-H, Miyazono K (1993) Cloning of a TGFb type I receptor that forms a heteromeric complex with the TGFb type II receptor. Cell 75:681–692PubMedGoogle Scholar
  50. Frederick JP, Liberati NT, Waddell DS, Shi Y, Wang XF (2004) Transforming growth factor beta-mediated transcriptional repression of c-myc is dependent on direct binding of Smad3 to a novel repressive Smad binding element. Mol Cell Biol 24:2546–2559PubMedGoogle Scholar
  51. Frutkin AD, Otsuka G, Stempien-Otero A, Sesti C, Du L, Jaffe M, Dichek HL, Pennington CJ, Edwards DR, Nieves-Cintron M, Minter D, Preusch M, Hu JH, Marie JC, Dichek DA (2009) TGF-[beta]1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 29:1251–1257PubMedGoogle Scholar
  52. Fu K, Corbley MJ, Sun L, Friedman JE, Shan F, Papadatos JL, Costa D, Lutterodt F, Sweigard H, Bowes S, Choi M, Boriack-Sjodin PA, Arduini RM, Sun D, Newman MN, Zhang X, Mead JN, Chuaqui CE, Cheung HK, Cornebise M, Carter MB, Josiah S, Singh J, Lee WC, Gill A, Ling LE (2008) SM16, an orally active TGF-beta type I receptor inhibitor prevents myofibroblast induction and vascular fibrosis in the rat carotid injury model. Arterioscler Thromb Vasc Biol 28:665–671PubMedGoogle Scholar
  53. Fujii S, Hopkins WE, Sobel BE (1991) Mechanisms contributing to increased synthesis of plasminogen activator inhibitor type 1 in endothelial cells by constituents of platelets and their implications for thrombolysis. Circulation 83:645–651PubMedGoogle Scholar
  54. Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200:500–503PubMedGoogle Scholar
  55. Gagarin D, Yang Z, Butler J, Wimmer M, Du B, Cahan P, McCaffrey TA (2005) Genomic profiling of acquired resistance to apoptosis in cells derived from human atherosclerotic lesions: potential role of STATs, cyclinD1, BAD, and Bcl-XL. J Mol Cell Cardiol 39:453–465PubMedGoogle Scholar
  56. Gojova A, Brun V, Esposito B, Cottrez F, Gourdy P, Ardouin P, Tedgui A, Mallat Z, Groux H (2003) Specific abrogation of transforming growth factor-beta signaling in T cells alters atherosclerotic lesion size and composition in mice. Blood 102:4052–4058PubMedGoogle Scholar
  57. Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, Dijke P ten (2002) Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J 21:1743–1753PubMedGoogle Scholar
  58. Grainger DJ (2004) Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis. Arterioscler Thromb Vasc Biol 24:399–404PubMedGoogle Scholar
  59. Grainger DJ (2007) TGF-beta and atherosclerosis in man. Cardiovasc Res 74:213–222PubMedGoogle Scholar
  60. Grainger DJ, Witchell CM, Watson JV, Metcalfe JC, Weissberg PL (1993) Heparin decreases the rate of proliferation of rat vascular smooth muscle cells by releasing transforming growth factor b-like activity from serum. Cardiovasc Res 27:2238–2247PubMedGoogle Scholar
  61. Grainger DJ, Kemp PR, Liu AC, Lawn RM, Metcalfe JC (1994) Activation of transforming growth factor-b is inhibited in transgenic apolipoprotein(a) mice. Nature 370:460–462PubMedGoogle Scholar
  62. Grainger DJ, Kemp PR, Metcalfe JC, Liu AC, Lawn RM, Williams NR, Grace AA, Schofield PM, Chauhan A (1995) The serum concentration of active transforming growth factor-b is severely depressed in advanced atherosclerosis. Nat Med 1:74–79PubMedGoogle Scholar
  63. Gratchev A, Kzhyshkowska J, Kannookadan S, Ochsenreiter M, Popova A, Yu X, Mamidi S, Stonehouse-Usselmann E, Muller-Molinet I, Gooi L, Goerdt S (2008) Activation of a TGF-beta-specific multistep gene expression program in mature macrophages requires glucocorticoid-mediated surface expression of TGF-beta receptor II. J Immunol 180:6553–6565PubMedGoogle Scholar
  64. Gressner OA, Lahme B, Siluschek M, Rehbein K, Weiskirchen R, Gressner AM (2009) Connective tissue growth factor is a Smad2 regulated amplifier of transforming growth factor beta actions in hepatocytes—but without modulating bone morphogenetic protein 7 signaling. Hepatology 49:2021–2030PubMedGoogle Scholar
  65. Grotendorst GR (1997) Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev 8:171–179PubMedGoogle Scholar
  66. Harats D, George J, Levy Y, Khamashta MA, Hughes GR, Shoenfeld Y (1999) Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus. QJM 92:57–59PubMedGoogle Scholar
  67. Hariri RJ, Alonso DR, Hajjar DP, Coletti D, Weksler ME (1986) Aging and atherosclerosis. I. Development of myointimal hyperplasia after endothelial injury. J Exp Med 164:1171–1178PubMedGoogle Scholar
  68. Hariri RJ, Hajjar DP, Coletti D, Alonso DR, Weksler ME, Rabellino E (1988) Aging and atherosclerosis. Cell cycle kinetics of young and old arterial smooth muscle cells. Am J Pathol 131:132–136PubMedGoogle Scholar
  69. He F, Zhao D, Deng F, Zhong H, Shi X, Yang J, Guo S, Cheng J, Huang G, Tang B, Wang Z, Chen X, Wang G, Zhang W, Zhang C, Wang X, Hu Q (2010) Association of TGF-beta1 gene polymorphisms in exon1 and blood levels with essential hypertension. Blood Press 19:225–233PubMedGoogle Scholar
  70. Heeg MH, Koziolek MJ, Vasko R, Schaefer L, Sharma K, Muller GA, Strutz F (2005) The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway. Kidney Int 68:96–109PubMedGoogle Scholar
  71. Heidland A, Sebekova K, Schinzel R (2001) Advanced glycation end products and the progressive course of renal disease. Am J Kidney Dis 38:S100–S106PubMedGoogle Scholar
  72. Heimark RL, Twardizik DR, Schwartz SM (1986) Inhibition of endothelial regeneration by type-b transforming growth factor from platelets. Science 233:1078–1080PubMedGoogle Scholar
  73. Hilker M, Langin T, Hake U, Schmid FX, Kuroczynski W, Lehr HA, Oelert H, Buerke M (2003) Gene expression profiling of human stenotic aorto-coronary bypass grafts by cDNA array analysis. Eur J Cardiothorac Surg 23:620–625PubMedGoogle Scholar
  74. Hogg N, Browning J, Howard T, Winterford C, Fitzpatrick D, Gobe G (1999) Apoptosis in vascular endothelial cells caused by serum deprivation, oxidative stress and transforming growth factor-beta. Endothelium 7:35–49PubMedGoogle Scholar
  75. Hyman KM, Seghezzi G, Pintucci G, Stellari G, Kim JH, Grossi EA, Galloway AC, Mignatti P (2002) Transforming growth factor-beta1 induces apoptosis in vascular endothelial cells by activation of mitogen-activated protein kinase. Surgery 132:173–179PubMedGoogle Scholar
  76. Ikedo H, Tamaki K, Ueda S, Kato S, Fujii M, Dijke P ten, Okuda S (2003) Smad protein and TGF-beta signaling in vascular smooth muscle cells. Int J Mol Med 11:645–650PubMedGoogle Scholar
  77. Jager SC de, Bermudez B, Bot I, Koenen RR, Bot M, Kavelaars A, Waard V de, Heijnen CJ, Muriana FJ, Weber C, Berkel TJ van, Kuiper J, Lee SJ, Abia R, Biessen EA (2011) Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis. J Exp Med 208:217–225PubMedGoogle Scholar
  78. Jeziorska M (2001) Transforming growth factor-betas and CD105 expression in calcification and bone formation in human atherosclerotic lesions. Z Kardiol 90 (Suppl 3):23–26PubMedGoogle Scholar
  79. Jiang X, Zeng H, Guo Y, Zhou Z, Tang B, Li F (2004) The expression of matrix metalloproteinases-9, transforming growth factor beta1 and transforming growth factor-beta receptor I in human atherosclerotic plaque and their relationship with plaque stability. Chin Med J Engl 117:1825–1829PubMedGoogle Scholar
  80. Jones JA, Spinale FG, Ikonomidis JS (2009) Transforming growth factor-beta signaling in thoracic aortic aneurysm development: a paradox in pathogenesis. J Vasc Res 46:119–137PubMedGoogle Scholar
  81. Joseph A, Ackerman D, Talley JD, Johnstone J, Kupersmith J (1993) Manifestations of coronary atherosclerosis in young trauma victims—an autopsy study. J Am Coll Cardiol 22:459–467PubMedGoogle Scholar
  82. Jung P, Menssen A, Mayr D, Hermeking H (2008) AP4 encodes a c-MYC-inducible repressor of p21. Proc Natl Acad Sci USA 105:15046–15051PubMedGoogle Scholar
  83. Kanzaki T, Tamura K, Takahashi K, Saito Y, Akikusa B, Oohashi H, Kasayuki N, Ueda M, Morisaki N (1995) In vivo effect of TGF-b1: enhanced intimal thickening by administration of TGF-b1 in rabbit arteries injured with a balloon catheter. Arterioscler Thromb 15:1951–1957Google Scholar
  84. Keeton MR, Curriden SA, Zonneveld AJ van, Loskutoff DJ (1991) Identification of regulatory sequences in the type 1 plasminogen activator gene responsive to transforming growth factor beta. J Biol Chem 266:23048–23052PubMedGoogle Scholar
  85. Khan R, Agrotis A, Bobik A (2007) Understanding the role of transforming growth factor-beta1 in intimal thickening after vascular injury. Cardiovasc Res 74:223–234PubMedGoogle Scholar
  86. Kim GY, Mercer SE, Ewton DZ, Yan Z, Jin K, Friedman E (2002) The stress-activated protein kinases p38 alpha and JNK1 stabilize p21(Cip1) by phosphorylation. J Biol Chem 277:29792–29802PubMedGoogle Scholar
  87. Kim JS, Kim JG, Moon MY, Jeon CY, Won HY, Kim HJ, Jeon YJ, Seo JY, Kim JI, Kim J, Lee JY, Kim PH, Park JB (2006) Transforming growth factor-beta1 regulates macrophage migration via RhoA. Blood 108:1821–1829PubMedGoogle Scholar
  88. Kletsas D, Stathakos D, Sorrentino V, Philipson L (1995) The growth-inhibitory block of TGF-beta is located close to the G1/S border in the cell cycle. Exp Cell Res 217:477–483PubMedGoogle Scholar
  89. Knoflach M, Bernhard D, Wick G (2005) Anti-HSP60 immunity is already associated with atherosclerosis early in life. Ann NY Acad Sci 1051:323–331PubMedGoogle Scholar
  90. Kohn EA, Du Z, Sato M, Van Schyndle CM, Welsh MA, Yang YA, Stuelten CH, Tang B, Ju W, Bottinger EP, Wakefield LM (2010) A novel approach for the generation of genetically modified mammary epithelial cell cultures yields new insights into TGF-beta signaling in the mammary gland. Breast Cancer Res 12:R83PubMedGoogle Scholar
  91. Kojima S, Nara K, Rifkin DB (1993) Requirement for transglutaminase in the activation of latent transforming growth factor-b in bovine endothelial cells. J Cell Biol 121:439–448PubMedGoogle Scholar
  92. Kolodgie FD, Narula J, Haider N, Virmani R (2001) Apoptosis in atherosclerosis. Does it contribute to plaque instability? Cardiol Clin 19:127–139PubMedGoogle Scholar
  93. Lawrence DA, Pircher R, Kryceve-Martineri C, Jullien P (1984) Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol 121:184–188PubMedGoogle Scholar
  94. Le Scolan E, Zhu Q, Wang L, Bandyopadhyay A, Javelaud D, Mauviel A, Sun L, Luo K (2008) Transforming growth factor-beta suppresses the ability of Ski to inhibit tumor metastasis by inducing its degradation. Cancer Res 68:3277–3285PubMedGoogle Scholar
  95. Lee J, Ko M, Joo CK (2008) Rho plays a key role in TGF-beta1-induced cytoskeletal rearrangement in human retinal pigment epithelium. J Cell Physiol 216:520–526PubMedGoogle Scholar
  96. Lin HY, Wang XF, Ng-Eaton E, Weinberg RA, Lodish HF (1992) Expression cloning of the TGF-b type II receptor, a functional transmembrane serine/threonine kinase. Cell 68:775–785PubMedGoogle Scholar
  97. Liu X, Sun Y, Constantinescu SN, Karam E, Weinberg RA, Lodish HF (1997) Transforming growth factor beta-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells. Proc Natl Acad Sci USA 94:10669–10674PubMedGoogle Scholar
  98. Liu X, Li P, Liu P, Xiong R, Zhang E, Chen X, Gu D, Zhao Y, Wang Z, Zhou Y (2008) The essential role for c-Ski in mediating TGF-beta1-induced bi-directional effects on skin fibroblast proliferation through a feedback loop. Biochem J 409:289–297PubMedGoogle Scholar
  99. Lomo J, Blomhoff HK, Beiske K, Stokke T, Smeland EB (1995) TGF-b1 and cyclic AMP promote apoptosis in resting human B lymphocytes. J Immunol 154:1634–1643PubMedGoogle Scholar
  100. Lundberg V, Stegmayr B, Asplund K, Eliasson M, Huhtasaari F (1997) Diabetes as a risk factor for myocardial infarction: population and gender perspectives. J Intern Med 241:485–492PubMedGoogle Scholar
  101. Lutgens E, Gijbels M, Smook M, Heeringa P, Gotwals P, Koteliansky VE, Daemen MJ (2002) Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression. Arterioscler Thromb Vasc Biol 22:975–982PubMedGoogle Scholar
  102. Lyons RM, Keski-Oja J, Moses HL (1988) Proteolytic activation of latent transforming growth factor-b from fibroblast-conditioned medium. J Cell Biol 106:1659–1665PubMedGoogle Scholar
  103. Lyons RM, Gentry LE, Purchio AF, Moses HL (1990) Mechanism of activation of latent recombinant transforming growth factor-b1 by plasmin. J Cell Biol 110:1361–1367PubMedGoogle Scholar
  104. Machado RD, Aldred MA, James V, Harrison RE, Patel B, Schwalbe EC, Gruenig E, Janssen B, Koehler R, Seeger W, Eickelberg O, Olschewski H, Elliott CG, Glissmeyer E, Carlquist J, Kim M, Torbicki A, Fijalkowska A, Szewczyk G, Parma J, Abramowicz MJ, Galie N, Morisaki H, Kyotani S, Nakanishi N, Morisaki T, Humbert M, Simonneau G, Sitbon O, Soubrier F, Coulet F, Morrell NW, Trembath RC (2006) Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat 27:121–132PubMedGoogle Scholar
  105. Madri JA, Reidy MA, Kocher O, Bell L (1989) Endothelial cell behavior after denudation injury is modulated by transforming growth factor-b1 and fibronectin. Lab Invest 60:755–764PubMedGoogle Scholar
  106. Majesky MW, Lindner V, Twardzik DR, Schwartz SM, Reidy MA (1991) Production of transforming growth factor-β1 during repair of arterial injury. J Clin Invest 88:904–910PubMedGoogle Scholar
  107. Mallat Z, Gojova A, Marchiol-Fournigault C, Esposito B, Kamate C, Merval R, Fradelizi D, Tedgui A (2001) Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ Res 89:930–934PubMedGoogle Scholar
  108. Malmstrom J, Lindberg H, Lindberg C, Bratt C, Wieslander E, Delander EL, Sarnstrand B, Burns JS, Mose-Larsen P, Fey S, Marko-Varga G (2004) Transforming growth factor-beta 1 specifically induce proteins involved in the myofibroblast contractile apparatus. Mol Cell Proteomics 3:466–477PubMedGoogle Scholar
  109. Matsumoto Y, Uwatoku T, Oi K, Abe K, Hattori T, Morishige K, Eto Y, Fukumoto Y, Nakamura K, Shibata Y, Matsuda T, Takeshita A, Shimokawa H (2004) Long-term inhibition of Rho-kinase suppresses neointimal formation after stent implantation in porcine coronary arteries: involvement of multiple mechanisms. Arterioscler Thromb Vasc Biol 24:181–186PubMedGoogle Scholar
  110. McCaffrey TA, Falcone DJ (1993) Evidence for an age-related dysfunction in the antiproliferative response to transforming growth factor-beta in vascular smooth muscle cells. Mol Biol Cell 4:315–322PubMedGoogle Scholar
  111. McCaffrey TA, Nicholson AC, Szabo PE, Weksler ME, Weksler BB (1988) Aging and arteriosclerosis. The increased proliferation of arterial smooth muscle cells isolated from old rats is associated with increased platelet-derived growth factor-like activity. J Exp Med 167:163–174PubMedGoogle Scholar
  112. McCaffrey TA, Falcone DJ, Brayton CF, Agarwal LA, Welt FG, Weksler BB (1989) Transforming growth factor-beta activity is potentiated by heparin via dissociation of the transforming growth factor-beta/alpha 2-macroglobulin inactive complex. J Cell Biol 109:441–448PubMedGoogle Scholar
  113. McCaffrey TA, Falcone DJ, Du B (1992) Transforming growth factor-beta 1 is a heparin-binding protein: identification of putative heparin-binding regions and isolation of heparins with varying affinity for TGF-beta 1. J Cell Physiol 152:430–440PubMedGoogle Scholar
  114. McCaffrey TA, Consigli S, Du B, Falcone DJ, Sanborn TA, Spokojny AM, Bush HL Jr (1995) Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1. J Clin Invest 96:2667–2675PubMedGoogle Scholar
  115. McCaffrey TA, Du B, Consigli S, Szabo P, Bray PJ, Hartner L, Weksler BB, Sanborn TA, Bergman G, Bush HL Jr (1997) Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells. J Clin Invest 100:2182–2188PubMedGoogle Scholar
  116. McCaffrey TA, Du B, Fu C, Bray PJ, Sanborn TA, Deutsch E, Tarazona N, Shaknovitch A, Newman G, Patterson C, Bush HL Jr (1999) The expression of TGF-beta receptors in human atherosclerosis: evidence for acquired resistance to apoptosis due to receptor imbalance. J Mol Cell Cardiol 31:1627–1642PubMedGoogle Scholar
  117. Mehta VY, Jorgensen MB, Raizner AE, Wolde-Tsadik G, Mahrer PR, Mansukhani P (1995) Spontaneous regression of restenosis: an angiographic study. J Am Coll Cardiol 26:696–702PubMedGoogle Scholar
  118. Meine TJ, Bauman RP, Yock PG, Rembert JC, Greenfield JC Jr (1999) Coronary artery restenosis after atherectomy is primarily due to negative remodeling. Am J Cardiol 84:141–146PubMedGoogle Scholar
  119. Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB, Brewer CC, Zalewski C, Kim HJ, Solomon B, Brooks BP, Gerber LH, Turner ML, Domingo DL, Hart TC, Graf J, Reynolds JC, Gropman A, Yanovski JA, Gerhard-Herman M, Collins FS, Nabel EG, Cannon RO 3rd, Gahl WA, Introne WJ (2008) Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 358:592–604PubMedGoogle Scholar
  120. Mintz GS, Pichard AD, Kent KM, Satler LF, Popma JJ, Leon MB (1998) Interrelation of coronary angiographic reference lumen size and intravascular ultrasound target lesion calcium. Am J Cardiol 81:387–391PubMedGoogle Scholar
  121. Miura M, Hata Y, Hirayama K, Kita T, Noda Y, Fujisawa K, Shimokawa H, Ishibashi T (2006) Critical role of the Rho-kinase pathway in TGF-beta2-dependent collagen gel contraction by retinal pigment epithelial cells. Exp Eye Res 82:849–859PubMedGoogle Scholar
  122. Mooradian DL, Lucas RC, Weatherbee JA, Furcht LT (1989) Transforming growth factor-b1 binds to immobilized fibronectin. J Cell Biochem 41:189–200PubMedGoogle Scholar
  123. Murphy-Ullrich JE, Schultz-Cherry S, Hook M (1992) Transforming growth factor-b complexes with thrombospondin. Mol Biol Cell 3:181–188PubMedGoogle Scholar
  124. Nabel EG, Shum L, Pompili VJ, Yang Z-Y, San H, Shu HB, Liptay S, Gold L, Gordon D, Derynck R, Nabel GJ (1993) Direct transfer of transforming growth factor b1 gene into arteries stimulates fibrocellular hyperplasia. Proc Natl Acad Sci USA 90:10759–10763PubMedGoogle Scholar
  125. Nagata H, Hatano E, Tada M, Murata M, Kitamura K, Asechi H, Narita M, Yanagida A, Tamaki N, Yagi S, Ikai I, Matsuzaki K, Uemoto S (2009) Inhibition of c-Jun NH2-terminal kinase switches Smad3 signaling from oncogenesis to tumor- suppression in rat hepatocellular carcinoma. Hepatology 49:1944–1953PubMedGoogle Scholar
  126. Nakashima Y, Fujii H, Sumiyoshi S, Wight TN, Sueishi K (2007) Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration. Arterioscler Thromb Vasc Biol 27:1159–1165PubMedGoogle Scholar
  127. Nikol S, Isner JM, Pickering JG, Kearney M, Leclerc G, Weir L (1992) Expression of transforming growth factor-b1 is increased in human vascular restenosis lesions. J Clin Invest 90:1582–1592PubMedGoogle Scholar
  128. Otsuka G, Agah R, Frutkin AD, Wight TN, Dichek DA (2006) Transforming growth factor beta 1 induces neointima formation through plasminogen activator inhibitor-1-dependent pathways. Arterioscler Thromb Vasc Biol 26:737–743PubMedGoogle Scholar
  129. Paralkar VM, Vukicevic S, Reddi AH (1991) Transforming growth factor-b type 1 binds to collagen IV of basement membrane matrix: implications for development. Dev Biol 143:303–308PubMedGoogle Scholar
  130. Pardali K, Kurisaki A, Moren A, Dijke P ten, Kardassis D, Moustakas A (2000) Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta. J Biol Chem 275:29244–29256PubMedGoogle Scholar
  131. Pardali K, Kowanetz M, Heldin CH, Moustakas A (2005) Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21(WAF1/Cip1). J Cell Physiol 204:260–272PubMedGoogle Scholar
  132. Pepper MS, Vassalli J-D, Orci L, Montesano R (1993) Biphasic effect of transforming growth factor-b1 on in vitro angiogenesis. Exp Cell Res 204:356–363PubMedGoogle Scholar
  133. Perros F, Dorfmuller P, Humbert M (2005) Current insights on the pathogenesis of pulmonary arterial hypertension. Semin Respir Crit Care Med 26:355–364PubMedGoogle Scholar
  134. Pierelli L, Marone M, Bonanno G, Mozzetti S, Rutella S, Morosetti R, Rumi C, Mancuso S, Leone G, Scambia G (2000) Modulation of bcl-2 and p27 in human primitive proliferating hematopoietic progenitors by autocrine TGF-beta1 is a cell cycle-independent effect and influences their hematopoietic potential. Blood 95:3001–3009PubMedGoogle Scholar
  135. Pollman M, Naumovski L, Gibbons G (1999) Vascular cell apoptosis: cell type-specific modulation by transforming growth factor-β1 in endothelial cells versus smooth muscle cells. Circulation 99:2019–2026PubMedGoogle Scholar
  136. Redondo S, Ruiz E, Padilla E, Gordillo-Moscoso A, Tejerina T (2007) Role of TGF-beta1 in vascular smooth muscle cell apoptosis induced by angiotensin II. Eur J Pharmacol 556:36–44PubMedGoogle Scholar
  137. Rembold C (1996) Could atherosclerosis originate from defective smooth muscle cell death? Perspect Biol Med 39:405–408PubMedGoogle Scholar
  138. Rich JN, Zhang M, Datto MB, Bigner DD, Wang XF (1999) Transforming growth factor-beta-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines. J Biol Chem 274:35053–35058PubMedGoogle Scholar
  139. Rivera P, Ocaranza MP, Lavandero S, Jalil JE (2007) Rho kinase activation and gene expression related to vascular remodeling in normotensive rats with high angiotensin I converting enzyme levels. Hypertension 50:792–798PubMedGoogle Scholar
  140. Robertson AK, Rudling M, Zhou X, Gorelik L, Flavell RA, Hansson GK (2003) Disruption of TGF-beta signaling in T cells accelerates atherosclerosis. J Clin Invest 112:1342–1350PubMedGoogle Scholar
  141. Rocha VZ, Libby P (2009) Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol 6:399–409PubMedGoogle Scholar
  142. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, Simone G de, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J (2011) Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation 123:e18-e209PubMedGoogle Scholar
  143. Rook GA (2001) The TGF-beta1 paradox in asthma. Trends Immunol 22:299–300PubMedGoogle Scholar
  144. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809PubMedGoogle Scholar
  145. Ross R, Masuda J, Raines EW, Gown AM, Katsuda S, Sasahara M, Malden LT, Masuko H, Sato H (1990) Localization of PDGF-B protein in macrophages in all stages of atherogenesis. Science 248:1009–1012PubMedGoogle Scholar
  146. Rossi P, Karsenty G, Roberts A, Roche NS, Sporn MB, Crombrugghe B (1988) A nuclear factor-1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-b. Cell 52:405–414PubMedGoogle Scholar
  147. Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC (2009) Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J 157:e112Google Scholar
  148. Saltis J, Agrotis A, Kanellakis P, Bobik A (1994) Developmentally regulated transforming growth factor-beta 1 action on vascular smooth muscle growth in the SHR. Clin Exp Pharmacol Physiol 21:149–152PubMedGoogle Scholar
  149. Saltis J, Agrotis A, Bobik A (1996) Regulation and interactions of transforming growth factor-beta with cardiovascular cells: implications for development and disease. Clin Exp Pharmacol Physiol 23:193–200PubMedGoogle Scholar
  150. Samarakoon R, Higgins PJ (2008) Integration of non-SMAD and SMAD signaling in TGF-beta1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells. Thromb Haemost 100:976–983PubMedGoogle Scholar
  151. Sarzani R, Brecher P, Chobanian AV (1989) Growth factor expression in aorta of normotensive and hypertensive rats. J Clin Invest 83:1404–1408PubMedGoogle Scholar
  152. Schmitt-Graff A, Desmouliere A, Gabbiani G (1994) Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity. Virchows Arch 425:3–24PubMedGoogle Scholar
  153. Schultz-Cherry S, Lawler J, Murphy-Ullrich JE (1994) The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-b. J Biol Chem 269:26783–26788PubMedGoogle Scholar
  154. Scott L, Kerr A, Haydock D, Merrilees M (1997) Subendothelial proteoglycan synthesis and transforming growth factor beta distribution correlate with susceptibility to atherosclerosis. J Vasc Res 34:365–377PubMedGoogle Scholar
  155. Seay U, Sedding D, Krick S, Hecker M, Seeger W, Eickelberg O (2005) Transforming growth factor-beta-dependent growth inhibition in primary vascular smooth muscle cells is p38-dependent. J Pharmacol Exp Ther 315:1005–1012PubMedGoogle Scholar
  156. Shen X, Li J, Hu PP, Waddell D, Zhang J, Wang XF (2001) The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation. J Biol Chem 276:15362–15368PubMedGoogle Scholar
  157. Shimada H, Staten NR, Rajagopalan LE (2011) TGF-beta1 mediated activation of Rho kinase induces TGF-beta2 and endothelin-1 expression in human hepatic stellate cells. J Hepatol 54:521–528PubMedGoogle Scholar
  158. Simionescu A, Philips K, Vyavahare N (2005) Elastin-derived peptides and TGF-beta1 induce osteogenic responses in smooth muscle cells. Biochem Biophys Res Commun 334:524–532PubMedGoogle Scholar
  159. Simper D, Stalboerger PG, Panetta CJ, Wang S, Caplice NM (2002) Smooth muscle progenitor cells in human blood. Circulation 106:1199–1204PubMedGoogle Scholar
  160. Sinha S, Hoofnagle MH, Kingston PA, McCanna ME, Owens GK (2004) Transforming growth factor-beta1 signaling contributes to development of smooth muscle cells from embryonic stem cells. Am J Physiol Cell Physiol 287:C1560–C1568PubMedGoogle Scholar
  161. Sinha S, Hoofnagle MH, Owens GK (2009) Derivation of contractile smooth muscle cells from embryonic stem cells. Methods Mol Biol 482:345–367PubMedGoogle Scholar
  162. Smith PC, Caceres M, Martinez J (2006) Induction of the myofibroblastic phenotype in human gingival fibroblasts by transforming growth factor-beta1: role of RhoA-ROCK and c-Jun N-terminal kinase signaling pathways. J Periodontal Res 41:418–425PubMedGoogle Scholar
  163. Sorrentino A, Thakur N, Grimsby S, Marcusson A, Bulow V von, Schuster N, Zhang S, Heldin CH, Landstrom M (2008) The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol 10:1199–1207PubMedGoogle Scholar
  164. Spender LC, Inman GJ (2009) TGF-beta induces growth arrest in Burkitt lymphoma cells via transcriptional repression of E2F-1. J Biol Chem 284:1435–1442PubMedGoogle Scholar
  165. Stefoni S, Cianciolo G, Donati G, Dormi A, Silvestri MG, Coli L, De Pascalis A, Iannelli S (2002) Low TGF-beta1 serum levels are a risk factor for atherosclerosis disease in ESRD patients. Kidney Int 61:324–335PubMedGoogle Scholar
  166. Stemerman MB, Weinstein R, Rowe JW, Maciag T, Fuhro R, Gardner R (1982) Vascular smooth muscle cell growth kinetics in vivo in aged rats. Proc Natl Acad Sci USA 79:3863–3866PubMedGoogle Scholar
  167. Strong J (1993) Natural history of aortic and coronary atherosclerotic lesions in youth. Findings from the PDAY Study. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb 13:1291–1298Google Scholar
  168. Strong JP (1995) Natural history and risk factors for early human atherogenesis. Pathobiological Determinants in Youth (PDAY) Research Group. Clin Chem 41:134–138PubMedGoogle Scholar
  169. Suwanabol PA, Kent KC, Liu B (2011) TGF-beta and restenosis revisited: a Smad link. J Surg Res 167:287–297PubMedGoogle Scholar
  170. Suzuki H, Yagi K, Kondo M, Kato M, Miyazono K, Miyazawa K (2004) c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements. Oncogene 23:5068–5076PubMedGoogle Scholar
  171. Takahata M, Inoue Y, Tsuda H, Imoto I, Koinuma D, Hayashi M, Ichikura T, Yamori T, Nagasaki K, Yoshida M, Matsuoka M, Morishita K, Yuki K, Hanyu A, Miyazawa K, Inazawa J, Miyazono K, Imamura T (2009) SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells. J Biol Chem 284:3334–3344PubMedGoogle Scholar
  172. Tashiro H, Shimokawa H, Sadamatu K, Yamamoto K (2002) Prognostic significance of plasma concentrations of transforming growth factor-beta in patients with coronary artery disease. Coron Artery Dis 13:139–143PubMedGoogle Scholar
  173. Tesseur I, Zhang H, Brecht W, Corn J, Gong JS, Yanagisawa K, Michikawa M, Weisgraber K, Huang Y, Wyss-Coray T (2009) Bioactive TGF-beta can associate with lipoproteins and is enriched in those containing apolipoprotein E3. J Neurochem 110:1254–1262PubMedGoogle Scholar
  174. Tian M, Schiemann WP (2009) The TGF-beta paradox in human cancer: an update. Future Oncol 5:259–271PubMedGoogle Scholar
  175. Topouzis S, Majesky MW (1996) Smooth muscle lineage diversity in the chick embryo. Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta. Dev Biol 178:430–445Google Scholar
  176. Tsai S, Hollenbeck ST, Ryer EJ, Edlin R, Yamanouchi D, Kundi R, Wang C, Liu B, Kent KC (2009) TGF-{beta} through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation. Am J Physiol Heart Circ Physiol 297:H540-H549PubMedGoogle Scholar
  177. Tsunawaki S, Sporn M, Ding A, Nathan C (1988) Deactivation of macrophages by transforming growth factor-beta. Nature 334:260–262PubMedGoogle Scholar
  178. Upton PD, Morrell NW (2009) TGF-beta and BMPR-II pharmacology—implications for pulmonary vascular diseases. Curr Opin Pharmacol 9:274–280PubMedGoogle Scholar
  179. Vaudo G, Bocci EB, Shoenfeld Y, Schillaci G, Wu R, Del Papa N, Vitali C, Delle Monache F, Marchesi S, Mannarino E, Gerli R (2005) Precocious intima-media thickening in patients with primary Sjogren's syndrome. Arthritis Rheum 52:3890–3897PubMedGoogle Scholar
  180. Vihert A (1976) Atherosclerosis of the aorta and coronary arteries in five towns. Bull World Health Organ 53:501–614PubMedGoogle Scholar
  181. Villines TC, Stanek EJ, Devine PJ, Turco M, Miller M, Weissman NJ, Griffen L, Taylor AJ (2010) The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol 55:2721–2726PubMedGoogle Scholar
  182. Vranken I, De Visscher G, Lebacq A, Verbeken E, Flameng W (2008) The recruitment of primitive Lin(−) Sca-1(+), CD34(+), c-kit(+) and CD271(+) cells during the early intraperitoneal foreign body reaction. Biomaterials 29:797–808PubMedGoogle Scholar
  183. Wakefield LM, Letterio JJ, Chen T, Danielpour D, Allison RS, Pai LH, Denicoff AM, Noone MH, Cowan KH, O'Shaughnessy JA et al (1995) Transforming growth factor-beta1 circulates in normal human plasma and is unchanged in advanced metastatic breast cancer. Clin Cancer Res 1:129–136PubMedGoogle Scholar
  184. Wan Y, Liu X, Kirschner MW (2001) The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction. Mol Cell 8:1027–1039PubMedGoogle Scholar
  185. Wang B, Omar A, Angelovska T, Drobic V, Rattan SG, Jones SC, Dixon IM (2007) Regulation of collagen synthesis by inhibitory Smad7 in cardiac myofibroblasts. Am J Physiol Heart Circ Physiol 293:H1282–H1290PubMedGoogle Scholar
  186. Wang N, Wang X, Xing C, Sun B, Yu X, Hu J, Liu J, Zeng M, Xiong M, Zhou S, Yang J (2010) Role of TGF-beta1 in bone matrix production in vascular smooth muscle cells induced by a high-phosphate environment. Nephron Exp Nephrol 115:e60–e68PubMedGoogle Scholar
  187. Weitzman S, Wang C, Rosamond WD, Chambless LE, Cooper LS, Shahar E, Goff DC (2004) Is diabetes an independent risk factor for mortality after myocardial infarction? The ARIC (Atherosclerosis Risk in Communities) Surveillance Study. Acta Diabetol 41:77–83PubMedGoogle Scholar
  188. Wen FQ, Kohyama T, Skold CM, Zhu YK, Liu X, Romberger DJ, Stoner J, Rennard SI (2002) Glucocorticoids modulate TGF-beta production. Inflammation 26:279–290PubMedGoogle Scholar
  189. Wolf YG, Rasmussen LM, Ruoslahti E (1994) Antibodies against transforming growth factor-β1 suppress intimal hyperplasia in a rat model. J Clin Invest 93:1172–1178PubMedGoogle Scholar
  190. Wrana JL, Attisano L, Carcamo J, Zentella A, Doody J, Laiho M, Wang XF, Massague J (1992) TGF beta signals through a heteromeric protein kinase receptor complex. Cell 71:1003–1014PubMedGoogle Scholar
  191. Wrana JL, Attisano L, Wieser R, Ventura F, Massague J (1994) Mechanism of activation of the TGF-b receptor. Nature 370:341–347PubMedGoogle Scholar
  192. Xu A, Kochanek K, Murphy S (2010) Deaths: final data for 2007. Natl Vital Statistics Reports 58:1–135Google Scholar
  193. Xu W, Angelis K, Danielpour D, Haddad MM, Bischof O, Campisi J, Stavnezer E, Medrano EE (2000) Ski acts as a co-repressor with Smad2 and Smad3 to regulate the response to type beta transforming growth factor. Proc Natl Acad Sci USA 97:5924–5929PubMedGoogle Scholar
  194. Yagi K, Furuhashi M, Aoki H, Goto D, Kuwano H, Sugamura K, Miyazono K, Kato M (2002) c-myc is a downstream target of the Smad pathway. J Biol Chem 277:854–861PubMedGoogle Scholar
  195. Yamaguchi Y, Mann DM, Ruoslahti E (1990) Negative regulation of transforming growth factor-b by the proteoglycan decorin. Nature 346:281–284PubMedGoogle Scholar
  196. Yamashita M, Fatyol K, Jin C, Wang X, Liu Z, Zhang YE (2008) TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta. Mol Cell 31:918–924PubMedGoogle Scholar
  197. Yang Z, Gagarin D, Ramezani A, Hawley RG, McCaffrey TA (2007) Resistance to fas-induced apoptosis in cells from human atherosclerotic lesions: elevated Bcl-XL inhibits apoptosis and caspase activation. J Vasc Res 44:483–494PubMedGoogle Scholar
  198. Yokote K, Kobayashi K, Saito Y (2006) The role of Smad3-dependent TGF-beta signal in vascular response to injury. Trends Cardiovasc Med 16:240–245PubMedGoogle Scholar
  199. Yuzawa H, Koinuma D, Maeda S, Yamamoto K, Miyazawa K, Imamura T (2009) Arkadia represses the expression of myoblast differentiation markers through degradation of Ski and the Ski-bound Smad complex in C2C12 myoblasts. Bone 44:53–60PubMedGoogle Scholar
  200. Zeller KI, Jegga AG, Aronow BJ, O'Donnell KA, Dang CV (2003) An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biol 4:R69PubMedGoogle Scholar
  201. Zhang YE (2009) Non-Smad pathways in TGF-beta signaling. Cell Res 19:128–139PubMedGoogle Scholar
  202. Zhou MS, Schuman IH, Jaimes EA, Raij L (2008) Renoprotection by statins is linked to a decrease in renal oxidative stress, TGF-beta, and fibronectin with concomitant increase in nitric oxide bioavailability. Am J Physiol Renal Physiol 295:F53–F59PubMedGoogle Scholar
  203. Zhou X, Johnston TP, Johansson D, Parini P, Funa K, Svensson J, Hansson GK (2009) Hypercholesterolemia leads to elevated TGF-beta1 activity and T helper 3-dependent autoimmune responses in atherosclerotic mice. Atherosclerosis 204:381–387PubMedGoogle Scholar
  204. Zohlnhofer D, Richter T, Neumann F, Nuhrenberg T, Wessely R, Brandl R, Murr A, Klein C, Baeuerle P (2001) Transcriptome analysis reveals a role of interferon-g in human neointima formation. Mol Cell 7:1059–1069PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Medicine, Division of Genomic MedicineThe George Washington University Medical CenterWashingtonUSA

Personalised recommendations