Interactions between Angiotensin II and PPAR-γ in cardiac myofibroblasts

Alterations in Angiotensin II (Ang II) and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) affect cardiovascular diseases, diabetes and metabolic disorders, suggesting that these two systems intersect at some common biochemical pathways. Elucidating common cellular signaling factors between these two systems are important for better design of combinatorial drugs for treating patients with these disorders. Inhibitors of Ang II and agonists of PPAR-γ appear to have similar and beneficial effects. Ang II, a pro-fibrotic factor, enhances collagen synthesis and contributes to adverse remodeling in case of hypertensive heart diseases that damage tissue structure and alter cardiac function. In contrast, increased PPAR-γ activity inhibits collagen synthesis, reduces fibrosis and adverse remodeling of the cardiac tissue. Treatments with Ang II blockers or with PPAR-γ agonists improve cardiac function. These effects are evident in cardiac myofibroblasts, which appear at the site of myocardial infarction. Cardiac myofibroblasts are the major cell types involved in tissue repair and remodeling. In this article, we review Ang II and PPAR-γ pathways operative in cardiac myofibroblasts and provide evidence for interactions between these two systems.