Angiotensin II and TGF-β in the Development of Cardiac Fibrosis, Myocyte Hypertrophy, and Heart Failure

Abstract

An explanation of the molecular mechanisms that trigger the development of pathological cardiac fibrosis, myocyte hypertrophy, and heart failure associated with common ailments such as chronic postinfarction has been sought at the bench top and clinic for the past 40years, and is a current topic of intensive investigative activity. During the past several years, awareness of the important role of molecular alterations in the cardiac myocyte and interstitium in cardiac physiology has burgeoned among investigators, and this has led to a focus on the role of cardiac fibrosis and myocyte hypertrophy in the development of heart failure. Among the information garnered from these studies is that growth factors including angiotensin II (AII) and transforming growth factorβ1 (TGF-β1 ), in particular, are believed to be involved in modulation of gene products specifically expressed by cardiac fibroblasts and cardiac myocytes in vitro, and their enhanced presence has been associated with myocardial stress and inappropriate cardiac growth and fibrosis in vivo. Although these growth factors certainly may act on the myocardium alone via specific signaling pathways, we will review evidence that the signals modulated by AII and TGF-β may be coordinated among cardiac fibroblasts and myocytes. In this context, cardiac myocyte hypertrophy and alteration of the cardiac interstitium, i.e., cardiac fibrosis, are examined.