The Role of TGF-beta Signaling in Myocardial Infarction and Cardiac Remodeling

Overview

Journal Cardiovasc Res

Specialty Cardiology & Vascular Diseases

Date 2006 Nov 18

PMID 17109837

Citations 441

Authors

Marcin Bujak

Nikolaos G Frangogiannis

Affiliations

Soon will be listed here.

Abstract

Transforming Growth Factor (TGF)-beta is markedly induced and rapidly activated in the infarcted myocardium. However, understanding of the exact role of TGF-beta signaling in the infarcted and remodeling heart has been hampered by the complex and unusual biology of TGF-beta activation and by the diversity of its effects eliciting multiple, and often opposing cellular responses. Experimental studies suggest that TGF-beta signaling may be crucial for repression of inflammatory gene synthesis in healing infarcts mediating resolution of the inflammatory infiltrate. In addition, TGF-beta may play an important role in modulating fibroblast phenotype and gene expression, promoting extracellular matrix deposition in the infarct by upregulating collagen and fibronectin synthesis and by decreasing matrix degradation through induction of protease inhibitors. TGF-beta is also a key mediator in the pathogenesis of hypertrophic and dilative ventricular remodeling by stimulating cardiomyocyte growth and by inducing interstitial fibrosis. In this review we summarize the current knowledge on the role of TGF-beta in infarct healing and cardiac remodeling.

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References

Werner F, Jain M, Feinberg M, Sibinga N, Pellacani A, Wiesel P . Transforming growth factor-beta 1 inhibition of macrophage activation is mediated via Smad3. J Biol Chem. 2000; 275(47):36653-8. DOI: 10.1074/jbc.M004536200. View

Hao J, Wang B, Jones S, Jassal D, Dixon I . Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro. Am J Physiol Heart Circ Physiol. 2000; 279(6):H3020-30. DOI: 10.1152/ajpheart.2000.279.6.H3020. View

Massague J . How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 2001; 1(3):169-78. DOI: 10.1038/35043051. View

Verrecchia F, Chu M, Mauviel A . Identification of novel TGF-beta /Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. J Biol Chem. 2001; 276(20):17058-62. DOI: 10.1074/jbc.M100754200. View

Frangogiannis N, Mendoza L, Lewallen M, Michael L, Smith C, Entman M . Induction and suppression of interferon-inducible protein 10 in reperfused myocardial infarcts may regulate angiogenesis. FASEB J. 2001; 15(8):1428-30. DOI: 10.1096/fj.00-0745fje. View

Bartram U, Molin D, Wisse L, Mohamad A, Sanford L, Doetschman T . Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in TGF-beta(2)-knockout mice. Circulation. 2001; 103(22):2745-52. DOI: 10.1161/01.cir.103.22.2745. View

Deten A, Holzl A, Leicht M, Barth W, Zimmer H . Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats. J Mol Cell Cardiol. 2001; 33(6):1191-207. DOI: 10.1006/jmcc.2001.1383. View

Yu C, Tipoe G, Lau C . Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial interstitial fibrosis after acute myocardial infarction. J Am Coll Cardiol. 2001; 38(4):1207-15. DOI: 10.1016/s0735-1097(01)01518-2. View

Baxter G, Mocanu M, Brar B, Latchman D, Yellon D . Cardioprotective effects of transforming growth factor-beta1 during early reoxygenation or reperfusion are mediated by p42/p44 MAPK. J Cardiovasc Pharmacol. 2001; 38(6):930-9. DOI: 10.1097/00005344-200112000-00015. View

10.

Mogford J, Tawil N, Chen A, Gies D, Xia Y, Mustoe T . Effect of age and hypoxia on TGFbeta1 receptor expression and signal transduction in human dermal fibroblasts: impact on cell migration. J Cell Physiol. 2002; 190(2):259-65. DOI: 10.1002/jcp.10060. View

11.

Schultz J, Witt S, Glascock B, Nieman M, Reiser P, Nix S . TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. J Clin Invest. 2002; 109(6):787-96. PMC: 150912. DOI: 10.1172/JCI14190. View

12.

Goumans M, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, Ten Dijke P . Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J. 2002; 21(7):1743-53. PMC: 125949. DOI: 10.1093/emboj/21.7.1743. View

13.

Frangogiannis N, Shimoni S, Chang S, Ren G, Shan K, Aggeli C . Evidence for an active inflammatory process in the hibernating human myocardium. Am J Pathol. 2002; 160(4):1425-33. PMC: 1867231. DOI: 10.1016/S0002-9440(10)62568-0. View

14.

Wang B, Hao J, Jones S, Yee M, Roth J, Dixon I . Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart. Am J Physiol Heart Circ Physiol. 2002; 282(5):H1685-96. DOI: 10.1152/ajpheart.00266.2001. View

15.

Frangogiannis N, Shimoni S, Chang S, Ren G, Dewald O, Gersch C . Active interstitial remodeling: an important process in the hibernating human myocardium. J Am Coll Cardiol. 2002; 39(9):1468-74. DOI: 10.1016/s0735-1097(02)01792-8. View

16.

Piek E, Heldin C, Ten Dijke P . Specificity, diversity, and regulation in TGF-beta superfamily signaling. FASEB J. 1999; 13(15):2105-24. View

17.

Murphy-Ullrich J, Poczatek M . Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev. 2000; 11(1-2):59-69. DOI: 10.1016/s1359-6101(99)00029-5. View

18.

Cohn J, Ferrari R, Sharpe N . Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000; 35(3):569-82. DOI: 10.1016/s0735-1097(99)00630-0. View

19.

Rosenkranz S, Flesch M, Amann K, Haeuseler C, Kilter H, Seeland U . Alterations of beta-adrenergic signaling and cardiac hypertrophy in transgenic mice overexpressing TGF-beta(1). Am J Physiol Heart Circ Physiol. 2002; 283(3):H1253-62. DOI: 10.1152/ajpheart.00578.2001. View

20.

Behfar A, Zingman L, Hodgson D, Rauzier J, Kane G, Terzic A . Stem cell differentiation requires a paracrine pathway in the heart. FASEB J. 2002; 16(12):1558-66. DOI: 10.1096/fj.02-0072com. View