Role of transforming growth factor-beta in the progression of heart failure.

Transforming growth factor (TGF-beta) is a multifunctional peptide growth factor that has an important role in the regulation of cell growth, differentiation, and repair in a variety of tissues. In mammals, the cytokine has three isoforms, TGF-beta1, TGF-beta2, and TGF-beta3. TGF- beta1 is up-regulated by Ang II and induction of TGF-beta1 causes cardiac fibrosis. The stimulus that triggers the expression of TGF-beta1 may be repeated causing continual injury, which is associated with an increase in the activity of Ang II in heart tissue. The interplay between Ang II and TGF-beta1 causes continued activation that may result in chronic hypertension and progressive myocardial fibrosis, leading to heart failure. The regulation of TGF-beta1 secretion and action involves complex transcriptional events. Overproduction of TGF-beta1 underlies tissue fibrosis. Understanding the actions and signaling transduction of TGF-beta could lead to the development of therapeutic options that may be effective in inhibiting myocardial fibrosis triggered by TGF-beta1 in heart failure.