ANGIOTENSIN-II SIGNALING PATHWAYS IN CARDIAC FIBROBLASTS - CONVENTIONAL VERSUS NOVEL MECHANISMS IN MEDIATING CARDIAC GROWTH AND FUNCTION

Angiotensin II has been demonstrated to be involved in the regulation of cellular growth of several tissues in response to developmental, ph ysiological, and pathophysiological processes. Angiotensin II has been implicated in the developmental growth of the left ventricle in the n eonate and remodeling of the heart following chronic hypertension and myocardial infarction. The inhibition of DNA synthesis and collagen de position in myocardial interstitium following myocardial infarction by angiotensin converting enzyme inhibitor, suggests that angiotensin II mediates interstitial and perivascular fibrobrosis by preventing fibr oblast proliferation. In the past, little attention was focused on the identity and functional roles of cardiac fibroblasts. Recent in vitro studies utilizing cultured cardiac fibroblasts demonstrate that angio tensin II, acting via the AT, receptor, initiates intracellular signal ling pathways in common with those of peptide growth factors. Below, w e describe growth-related aspects of cardiac fibroblasts with respect to angiotensin II receptors, conventional and novel signal transductio n systems, secretion of extracellular matrix proteins and growth facto rs, and localization of renin-angiotensin system components.