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

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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.

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References

  • Abe R, Donnelly SC, Peng T, Bucala R, Metz CN (2001) Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 166:7556–7562

    PubMed  CAS  Google Scholar 

  • 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 150:3109–3118

    PubMed  CAS  Google Scholar 

  • Akhurst RJ (2004) TGF[beta] signaling in health and disease. Nat Genet 36:790–792

    PubMed  CAS  Google Scholar 

  • 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 92:3239–3243

    PubMed  CAS  Google Scholar 

  • 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 109:3137–3145

    PubMed  CAS  Google Scholar 

  • 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 102:1217–1223

    PubMed  CAS  Google Scholar 

  • 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 120:61–72

    PubMed  Google Scholar 

  • 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 3:221–225

    PubMed  CAS  Google Scholar 

  • 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 63:515–524

    PubMed  CAS  Google Scholar 

  • 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 37:373–380

    PubMed  Google Scholar 

  • Bell JA, Bell L (1989) Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells. Circ Res 65:1057–1065

    PubMed  CAS  Google Scholar 

  • 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 81:591–599

    PubMed  CAS  Google Scholar 

  • 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 100:15548–15553

    PubMed  CAS  Google Scholar 

  • Bjorkerud S (1991) Effects of transforming growth factor-b1 on human arterial smooth muscle cells in vitro. Arteriosclerosis 11:892–902

    CAS  Google Scholar 

  • Bobik A (2006) Transforming growth factor-betas and vascular disorders. Arterioscler Thromb Vasc Biol 26:1712–1720

    PubMed  CAS  Google Scholar 

  • 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 99:2883–2891

    PubMed  CAS  Google Scholar 

  • 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 13:1449–1455

    CAS  Google Scholar 

  • 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 146:1059–1064

    PubMed  CAS  Google Scholar 

  • 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 72:2628–2634

    PubMed  CAS  Google Scholar 

  • 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 140:454–463

    PubMed  Google Scholar 

  • Boyd FT, Cheifetz S, Andres J, Laiho M, Massague J (1990) Transforming growth factor-b receptors and binding proteoglycans. J Cell Sci Suppl 13:131–138

    PubMed  CAS  Google Scholar 

  • 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 19:1180–1189

    PubMed  CAS  Google Scholar 

  • 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 18:1249–1251

    PubMed  CAS  Google Scholar 

  • 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–H395

    PubMed  CAS  Google Scholar 

  • 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 69:589–602

    PubMed  CAS  Google Scholar 

  • 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 285:26798–26805

    PubMed  CAS  Google Scholar 

  • 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 59:446–448

    PubMed  CAS  Google Scholar 

  • 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 120:3509–3521

    PubMed  CAS  Google Scholar 

  • 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 215:223–233

    PubMed  CAS  Google Scholar 

  • 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 84:5287–5291

    PubMed  CAS  Google Scholar 

  • 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 389:217–223

    PubMed  CAS  Google Scholar 

  • 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 35:2253–2257

    PubMed  CAS  Google Scholar 

  • 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 97:9498–9503

    PubMed  CAS  Google Scholar 

  • 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 21:555–559

    PubMed  CAS  Google Scholar 

  • 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 270:28623–28628

    PubMed  CAS  Google Scholar 

  • 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 260:1344–1348

    PubMed  CAS  Google Scholar 

  • 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 49:1289–1295

    PubMed  Google Scholar 

  • Enos WF Jr, Beyer JC, Holmes RH (1955) Pathogenesis of coronary disease in American soldiers killed in Korea. J Am Med Assoc 158:912–914

    PubMed  Google Scholar 

  • 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 423:293–298

    PubMed  CAS  Google Scholar 

  • Evans RA, Tian YC, Steadman R, Phillips AO (2003) TGF-beta1-mediated fibroblast-myofibroblast terminal differentiation—the role of Smad proteins. Exp Cell Res 282:90–100

    PubMed  CAS  Google Scholar 

  • Fadini GP, Tjwa M (2010) A role for TGF-beta in transforming endothelial progenitor cells into neointimal smooth muscle cells. Atherosclerosis 211:32–35

    PubMed  CAS  Google Scholar 

  • 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 155:595–605

    PubMed  CAS  Google Scholar 

  • 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 268:11951–11958

    PubMed  CAS  Google Scholar 

  • 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 263:87–89

    Google Scholar 

  • Feinberg MW, Jain MK (2005) Role of transforming growth factor-beta1/Smads in regulating vascular inflammation and atherogenesis. Panminerva Med 47:169–186

    PubMed  CAS  Google Scholar 

  • 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 279:16388–16393

    PubMed  CAS  Google Scholar 

  • 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 108:653–660

    PubMed  CAS  Google Scholar 

  • 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) 588:3971–3982

    CAS  Google Scholar 

  • 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 75:681–692

    PubMed  CAS  Google Scholar 

  • 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 24:2546–2559

    PubMed  CAS  Google Scholar 

  • 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 29:1251–1257

    PubMed  CAS  Google Scholar 

  • 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 28:665–671

    PubMed  CAS  Google Scholar 

  • 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 83:645–651

    PubMed  CAS  Google Scholar 

  • Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200:500–503

    PubMed  CAS  Google Scholar 

  • 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 39:453–465

    PubMed  CAS  Google Scholar 

  • 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 102:4052–4058

    PubMed  CAS  Google Scholar 

  • 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 21:1743–1753

    PubMed  CAS  Google Scholar 

  • Grainger DJ (2004) Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis. Arterioscler Thromb Vasc Biol 24:399–404

    PubMed  CAS  Google Scholar 

  • Grainger DJ (2007) TGF-beta and atherosclerosis in man. Cardiovasc Res 74:213–222

    PubMed  CAS  Google Scholar 

  • 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 27:2238–2247

    PubMed  CAS  Google Scholar 

  • 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 370:460–462

    PubMed  CAS  Google Scholar 

  • 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 1:74–79

    PubMed  CAS  Google Scholar 

  • 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 180:6553–6565

    PubMed  CAS  Google Scholar 

  • 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 49:2021–2030

    PubMed  CAS  Google Scholar 

  • Grotendorst GR (1997) Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev 8:171–179

    PubMed  CAS  Google Scholar 

  • Harats D, George J, Levy Y, Khamashta MA, Hughes GR, Shoenfeld Y (1999) Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus. QJM 92:57–59

    PubMed  CAS  Google Scholar 

  • 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 164:1171–1178

    PubMed  CAS  Google Scholar 

  • 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 131:132–136

    PubMed  CAS  Google Scholar 

  • 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 19:225–233

    PubMed  CAS  Google Scholar 

  • 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 68:96–109

    PubMed  CAS  Google Scholar 

  • Heidland A, Sebekova K, Schinzel R (2001) Advanced glycation end products and the progressive course of renal disease. Am J Kidney Dis 38:S100–S106

    PubMed  CAS  Google Scholar 

  • Heimark RL, Twardizik DR, Schwartz SM (1986) Inhibition of endothelial regeneration by type-b transforming growth factor from platelets. Science 233:1078–1080

    PubMed  CAS  Google Scholar 

  • 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 23:620–625

    PubMed  Google Scholar 

  • 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 7:35–49

    PubMed  CAS  Google Scholar 

  • 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 132:173–179

    PubMed  Google Scholar 

  • 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 11:645–650

    PubMed  CAS  Google Scholar 

  • 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 208:217–225

    PubMed  Google Scholar 

  • Jeziorska M (2001) Transforming growth factor-betas and CD105 expression in calcification and bone formation in human atherosclerotic lesions. Z Kardiol 90 (Suppl 3):23–26

    PubMed  Google Scholar 

  • 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 117:1825–1829

    PubMed  CAS  Google Scholar 

  • Jones JA, Spinale FG, Ikonomidis JS (2009) Transforming growth factor-beta signaling in thoracic aortic aneurysm development: a paradox in pathogenesis. J Vasc Res 46:119–137

    PubMed  CAS  Google Scholar 

  • 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 22:459–467

    PubMed  CAS  Google Scholar 

  • Jung P, Menssen A, Mayr D, Hermeking H (2008) AP4 encodes a c-MYC-inducible repressor of p21. Proc Natl Acad Sci USA 105:15046–15051

    PubMed  CAS  Google Scholar 

  • 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 15:1951–1957

    CAS  Google Scholar 

  • 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 266:23048–23052

    PubMed  CAS  Google Scholar 

  • Khan R, Agrotis A, Bobik A (2007) Understanding the role of transforming growth factor-beta1 in intimal thickening after vascular injury. Cardiovasc Res 74:223–234

    PubMed  CAS  Google Scholar 

  • 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 277:29792–29802

    PubMed  CAS  Google Scholar 

  • 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 108:1821–1829

    PubMed  CAS  Google Scholar 

  • 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 217:477–483

    PubMed  CAS  Google Scholar 

  • Knoflach M, Bernhard D, Wick G (2005) Anti-HSP60 immunity is already associated with atherosclerosis early in life. Ann NY Acad Sci 1051:323–331

    PubMed  CAS  Google Scholar 

  • 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:R83

    PubMed  Google Scholar 

  • 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 121:439–448

    PubMed  CAS  Google Scholar 

  • Kolodgie FD, Narula J, Haider N, Virmani R (2001) Apoptosis in atherosclerosis. Does it contribute to plaque instability? Cardiol Clin 19:127–139

    PubMed  CAS  Google Scholar 

  • Lawrence DA, Pircher R, Kryceve-Martineri C, Jullien P (1984) Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol 121:184–188

    PubMed  CAS  Google Scholar 

  • 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 68:3277–3285

    PubMed  Google Scholar 

  • 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 216:520–526

    PubMed  CAS  Google Scholar 

  • 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 68:775–785

    PubMed  CAS  Google Scholar 

  • 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 94:10669–10674

    PubMed  CAS  Google Scholar 

  • 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 409:289–297

    PubMed  CAS  Google Scholar 

  • 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 154:1634–1643

    PubMed  CAS  Google Scholar 

  • 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 241:485–492

    PubMed  CAS  Google Scholar 

  • 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 22:975–982

    PubMed  CAS  Google Scholar 

  • Lyons RM, Keski-Oja J, Moses HL (1988) Proteolytic activation of latent transforming growth factor-b from fibroblast-conditioned medium. J Cell Biol 106:1659–1665

    PubMed  CAS  Google Scholar 

  • Lyons RM, Gentry LE, Purchio AF, Moses HL (1990) Mechanism of activation of latent recombinant transforming growth factor-b1 by plasmin. J Cell Biol 110:1361–1367

    PubMed  CAS  Google Scholar 

  • 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 27:121–132

    PubMed  CAS  Google Scholar 

  • 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 60:755–764

    PubMed  CAS  Google Scholar 

  • 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 88:904–910

    PubMed  CAS  Google Scholar 

  • 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 89:930–934

    PubMed  CAS  Google Scholar 

  • 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 3:466–477

    PubMed  Google Scholar 

  • 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 24:181–186

    PubMed  CAS  Google Scholar 

  • 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 4:315–322

    PubMed  CAS  Google Scholar 

  • 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 167:163–174

    PubMed  CAS  Google Scholar 

  • 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 109:441–448

    PubMed  CAS  Google Scholar 

  • 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 152:430–440

    PubMed  CAS  Google Scholar 

  • 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 96:2667–2675

    PubMed  CAS  Google Scholar 

  • 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 100:2182–2188

    PubMed  CAS  Google Scholar 

  • 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 31:1627–1642

    PubMed  CAS  Google Scholar 

  • 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 26:696–702

    PubMed  CAS  Google Scholar 

  • 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 84:141–146

    PubMed  CAS  Google Scholar 

  • 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 358:592–604

    PubMed  CAS  Google Scholar 

  • 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 81:387–391

    PubMed  CAS  Google Scholar 

  • 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 82:849–859

    PubMed  CAS  Google Scholar 

  • Mooradian DL, Lucas RC, Weatherbee JA, Furcht LT (1989) Transforming growth factor-b1 binds to immobilized fibronectin. J Cell Biochem 41:189–200

    PubMed  CAS  Google Scholar 

  • Murphy-Ullrich JE, Schultz-Cherry S, Hook M (1992) Transforming growth factor-b complexes with thrombospondin. Mol Biol Cell 3:181–188

    PubMed  CAS  Google Scholar 

  • 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 90:10759–10763

    PubMed  CAS  Google Scholar 

  • 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 49:1944–1953

    PubMed  CAS  Google Scholar 

  • 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 27:1159–1165

    PubMed  CAS  Google Scholar 

  • 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 90:1582–1592

    PubMed  CAS  Google Scholar 

  • 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 26:737–743

    PubMed  CAS  Google Scholar 

  • 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 143:303–308

    PubMed  CAS  Google Scholar 

  • 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 275:29244–29256

    PubMed  CAS  Google Scholar 

  • 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 204:260–272

    PubMed  CAS  Google Scholar 

  • Pepper MS, Vassalli J-D, Orci L, Montesano R (1993) Biphasic effect of transforming growth factor-b1 on in vitro angiogenesis. Exp Cell Res 204:356–363

    PubMed  CAS  Google Scholar 

  • Perros F, Dorfmuller P, Humbert M (2005) Current insights on the pathogenesis of pulmonary arterial hypertension. Semin Respir Crit Care Med 26:355–364

    PubMed  Google Scholar 

  • 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 95:3001–3009

    PubMed  CAS  Google Scholar 

  • 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 99:2019–2026

    PubMed  CAS  Google Scholar 

  • 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 556:36–44

    PubMed  CAS  Google Scholar 

  • Rembold C (1996) Could atherosclerosis originate from defective smooth muscle cell death? Perspect Biol Med 39:405–408

    PubMed  CAS  Google Scholar 

  • 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 274:35053–35058

    PubMed  CAS  Google Scholar 

  • 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 50:792–798

    PubMed  CAS  Google Scholar 

  • 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 112:1342–1350

    PubMed  CAS  Google Scholar 

  • Rocha VZ, Libby P (2009) Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol 6:399–409

    PubMed  CAS  Google Scholar 

  • 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-e209

    PubMed  Google Scholar 

  • Rook GA (2001) The TGF-beta1 paradox in asthma. Trends Immunol 22:299–300

    PubMed  CAS  Google Scholar 

  • Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809

    PubMed  CAS  Google Scholar 

  • 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 248:1009–1012

    PubMed  CAS  Google Scholar 

  • 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 52:405–414

    PubMed  CAS  Google Scholar 

  • 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:e112

    Google Scholar 

  • 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 21:149–152

    PubMed  CAS  Google Scholar 

  • 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 23:193–200

    PubMed  CAS  Google Scholar 

  • 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 100:976–983

    PubMed  CAS  Google Scholar 

  • Sarzani R, Brecher P, Chobanian AV (1989) Growth factor expression in aorta of normotensive and hypertensive rats. J Clin Invest 83:1404–1408

    PubMed  CAS  Google Scholar 

  • Schmitt-Graff A, Desmouliere A, Gabbiani G (1994) Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity. Virchows Arch 425:3–24

    PubMed  CAS  Google Scholar 

  • 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 269:26783–26788

    PubMed  CAS  Google Scholar 

  • 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 34:365–377

    PubMed  CAS  Google Scholar 

  • 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 315:1005–1012

    PubMed  CAS  Google Scholar 

  • 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 276:15362–15368

    PubMed  CAS  Google Scholar 

  • 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 54:521–528

    PubMed  CAS  Google Scholar 

  • Simionescu A, Philips K, Vyavahare N (2005) Elastin-derived peptides and TGF-beta1 induce osteogenic responses in smooth muscle cells. Biochem Biophys Res Commun 334:524–532

    PubMed  CAS  Google Scholar 

  • Simper D, Stalboerger PG, Panetta CJ, Wang S, Caplice NM (2002) Smooth muscle progenitor cells in human blood. Circulation 106:1199–1204

    PubMed  CAS  Google Scholar 

  • 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–C1568

    PubMed  CAS  Google Scholar 

  • Sinha S, Hoofnagle MH, Owens GK (2009) Derivation of contractile smooth muscle cells from embryonic stem cells. Methods Mol Biol 482:345–367

    PubMed  CAS  Google Scholar 

  • 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 41:418–425

    PubMed  CAS  Google Scholar 

  • 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 10:1199–1207

    PubMed  CAS  Google Scholar 

  • Spender LC, Inman GJ (2009) TGF-beta induces growth arrest in Burkitt lymphoma cells via transcriptional repression of E2F-1. J Biol Chem 284:1435–1442

    PubMed  CAS  Google Scholar 

  • 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 61:324–335

    PubMed  CAS  Google Scholar 

  • 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 79:3863–3866

    PubMed  CAS  Google Scholar 

  • 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 13:1291–1298

    Google Scholar 

  • Strong JP (1995) Natural history and risk factors for early human atherogenesis. Pathobiological Determinants in Youth (PDAY) Research Group. Clin Chem 41:134–138

    PubMed  CAS  Google Scholar 

  • Suwanabol PA, Kent KC, Liu B (2011) TGF-beta and restenosis revisited: a Smad link. J Surg Res 167:287–297

    PubMed  CAS  Google Scholar 

  • 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 23:5068–5076

    PubMed  CAS  Google Scholar 

  • 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 284:3334–3344

    PubMed  CAS  Google Scholar 

  • 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 13:139–143

    PubMed  Google Scholar 

  • 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 110:1254–1262

    PubMed  CAS  Google Scholar 

  • Tian M, Schiemann WP (2009) The TGF-beta paradox in human cancer: an update. Future Oncol 5:259–271

    PubMed  CAS  Google Scholar 

  • 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 178:430–445

    CAS  Google Scholar 

  • 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-H549

    PubMed  CAS  Google Scholar 

  • Tsunawaki S, Sporn M, Ding A, Nathan C (1988) Deactivation of macrophages by transforming growth factor-beta. Nature 334:260–262

    PubMed  CAS  Google Scholar 

  • Upton PD, Morrell NW (2009) TGF-beta and BMPR-II pharmacology—implications for pulmonary vascular diseases. Curr Opin Pharmacol 9:274–280

    PubMed  CAS  Google Scholar 

  • 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 52:3890–3897

    PubMed  Google Scholar 

  • Vihert A (1976) Atherosclerosis of the aorta and coronary arteries in five towns. Bull World Health Organ 53:501–614

    PubMed  CAS  Google Scholar 

  • 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 55:2721–2726

    PubMed  Google Scholar 

  • 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 29:797–808

    PubMed  CAS  Google Scholar 

  • 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 1:129–136

    PubMed  CAS  Google Scholar 

  • Wan Y, Liu X, Kirschner MW (2001) The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction. Mol Cell 8:1027–1039

    PubMed  CAS  Google Scholar 

  • 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–H1290

    PubMed  CAS  Google Scholar 

  • 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–e68

    PubMed  CAS  Google Scholar 

  • 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 41:77–83

    PubMed  CAS  Google Scholar 

  • Wen FQ, Kohyama T, Skold CM, Zhu YK, Liu X, Romberger DJ, Stoner J, Rennard SI (2002) Glucocorticoids modulate TGF-beta production. Inflammation 26:279–290

    PubMed  CAS  Google Scholar 

  • Wolf YG, Rasmussen LM, Ruoslahti E (1994) Antibodies against transforming growth factor-β1 suppress intimal hyperplasia in a rat model. J Clin Invest 93:1172–1178

    PubMed  CAS  Google Scholar 

  • 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 71:1003–1014

    PubMed  CAS  Google Scholar 

  • Wrana JL, Attisano L, Wieser R, Ventura F, Massague J (1994) Mechanism of activation of the TGF-b receptor. Nature 370:341–347

    PubMed  CAS  Google Scholar 

  • Xu A, Kochanek K, Murphy S (2010) Deaths: final data for 2007. Natl Vital Statistics Reports 58:1–135

    Google Scholar 

  • 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 97:5924–5929

    PubMed  CAS  Google Scholar 

  • 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 277:854–861

    PubMed  CAS  Google Scholar 

  • Yamaguchi Y, Mann DM, Ruoslahti E (1990) Negative regulation of transforming growth factor-b by the proteoglycan decorin. Nature 346:281–284

    PubMed  CAS  Google Scholar 

  • 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 31:918–924

    PubMed  CAS  Google Scholar 

  • 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 44:483–494

    PubMed  CAS  Google Scholar 

  • Yokote K, Kobayashi K, Saito Y (2006) The role of Smad3-dependent TGF-beta signal in vascular response to injury. Trends Cardiovasc Med 16:240–245

    PubMed  CAS  Google Scholar 

  • 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 44:53–60

    PubMed  CAS  Google Scholar 

  • 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:R69

    PubMed  Google Scholar 

  • Zhang YE (2009) Non-Smad pathways in TGF-beta signaling. Cell Res 19:128–139

    PubMed  CAS  Google Scholar 

  • 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–F59

    PubMed  CAS  Google Scholar 

  • 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 204:381–387

    PubMed  CAS  Google Scholar 

  • 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 7:1059–1069

    PubMed  CAS  Google Scholar 

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Toma, I., McCaffrey, T.A. Transforming growth factor-β and atherosclerosis: interwoven atherogenic and atheroprotective aspects. Cell Tissue Res 347, 155–175 (2012). https://doi.org/10.1007/s00441-011-1189-3

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