Cross talk between angiotensin II and PPAR-γ during cardiac remodeling

Cardiac remodeling is characterized by excessive production of extracellular matrix (ECM) proteins by specialized cells referred to as cardiac myofibroblasts. Cardiac myofibroblasts function both as autocrine and paracrine cell types secreting pro-fibrotic factors, which accelerates production of ECM proteins. Among these pro-fibrotic factors, Angiotensin II (Ang II) plays a predominant role by influencing multiple pathways that promote ECM production and adverse remodeling. Agents that block Ang II and its receptors reduce ECM synthesis and improve cardiac function. These effects are similar to those obtained by peroxisome proliferators activated receptor-γ (PPAR-γ) agonists. Both Ang II receptor inhibitors and PPAR-γ agonists appear to have similar beneficial effects on cardiovascular diseases, diabetes and metabolic syndromes. These similar effects suggest cross-regulatory interactions between Ang II and PPAR-γ pathways. The significance of these interactions regulating cardiac remodeling is discussed in this chapter.