Angiotensin Receptor Blockers in Chronic Heart Failure: Clinical Implications and Molecular Mechanisms

Angiotensin II is the main effector molecule of the renin-angiotensin system and has been implicated in regulating cell growth, inflammation and fibrosis, contributing to cardiac remodeling, growth and apoptosis. Cardiac remodeling is the determinant in the progression of heart failure. Thus, chronic activation of the renin-angiotensin system plays an important role in the structural and functional pathogeneses of heart failure. To date, most of the known physiological effects of Ang II in adult tissues are attributable to the AT1R although recent progress has shown some important actions of the involvement of AT2R. Clinical trials have documented consistent mortality and morbidity benefits of angiotensin receptor blockers in patients with chronic heart failure. Recent experimental studies link the beneficial effects of inhibiting Ang II to transforming growth factor-β1. Extracellular matrix accumulation in cardiovascular system is involved in vascular and cardiac hypertrophy and heart failure. Therefore, Ang II and TGF-β1 cross talk provides the pathophysiological insight in the development of cardiac fibrosis and heart failure. These molecular interactions might provide the beneficial effects of chronic AT1 receptor blockade, a known antifibrotic strategy, in patient with heart failure.