The role of TGF-β in hypertrophy, fibrosis and post-infarction cardiac remodeling. A: TGF-β transduces hypertrophic signals in cardiomyocytes and induces myofibroblast transdifferentiation, while promoting matrix deposition and preservation. Although TGF-β inhibition in the pressure-overloaded ventricle may attenuate hypertrophy and reduce fibrosis protecting from diastolic dysfunction, complete loss of TGF-β signaling may result in unopposed matrix degradation, cardiac dilation and systolic dysfunction. B: In the infarcted heart TGF-β may serve as the “master switch” that regulates transition from the inflammatory phase to scar formation. TGF-β suppresses inflammatory mediator synthesis by macrophages while enhancing myofibroblast transdifferentiation and matrix deposition. Thus, timing is a crucial determinant of outcome in pharmacologic interventions targeting the TGF-β system following myocardial infarction.