Figure 1.

TGF-β contribution to cardiac fibrotic events. (A) TGF-β affects phenotype along with operation in every cell somehow engaged in myocardial fibrotic event. Straightforward effects on conversing fibroblast (F) to myofibroblast (MF) and activating myofibroblast can be probably of more importance, but fibrogenesis caused by TGF-βs can further relate with its impacts on the phenotype of macrophage (Ma), differentiation and function of lymphocyte (L), and cardiomyocyte (CM) viability, as well as gene expression. Apart from that, TGF-β can encourage pericyte (P) to fibroblast transformation and endothelial-to-mesenchymal transdifferentiation, when induced by vascular cells to express fibrosis-associated genes. (B) TGF-βs regulate phenotypes of the cells through activation of Smad-related together with non-Smad signaling pathways. (C) TGF-β/Smad3 signaling effect on CFs. Current researches taking advantage of loss-of-function procedures associated with specific cells drew conclusion that activating Smad3 contributes significantly to the formation of organized myofibroblast arrays after myocardial infarction. Lack of Smad3 in fibroblasts deranges infarcted heart reparations, resulting in higher risks of late cardiac rupture and undesirable chamber dilation. The evidence points out the reparative operation of fibroblasts activated in the infarcted myocardium. Mediation of the Smad3 effects is being carried out by the integrin–ROS axis arousal. This figure was adapted from Frangogiannis (15).