The role of TGF-β signaling in myocardial infarction and cardiac remodeling

M Bujak, NG Frangogiannis - Cardiovascular research, 2007 - academic.oup.com
Cardiovascular research, 2007academic.oup.com
Abstract Transforming Growth Factor (TGF)-β is markedly induced and rapidly activated in
the infarcted myocardium. However, understanding of the exact role of TGF-β signaling in
the infarcted and remodeling heart has been hampered by the complex and unusual biology
of TGF-β activation and by the diversity of its effects eliciting multiple, and often opposing
cellular responses. Experimental studies suggest that TGF-β signaling may be crucial for
repression of inflammatory gene synthesis in healing infarcts mediating resolution of the …
Abstract
Transforming Growth Factor (TGF)-β is markedly induced and rapidly activated in the infarcted myocardium. However, understanding of the exact role of TGF-β signaling in the infarcted and remodeling heart has been hampered by the complex and unusual biology of TGF-β activation and by the diversity of its effects eliciting multiple, and often opposing cellular responses. Experimental studies suggest that TGF-β signaling may be crucial for repression of inflammatory gene synthesis in healing infarcts mediating resolution of the inflammatory infiltrate. In addition, TGF-β 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-β 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-β in infarct healing and cardiac remodeling.
Oxford University Press