ß-Adrenergic Receptor-Stimulated Cardiac Myocyte Apoptosis: Role of ß1 Integrins.

Increased sympathetic nerve activity to the myocardium is a central feature in patients with heart failure. Accumulation of catecholamines plays an important role in the pathogenesis of heart disease. Acting via ß-adrenergic receptors (ß-AR), catecholamines (norepinephrine and isoproterenol) increase cardiac myocyte apoptosis in vitro and in vivo. Specifically, ß(1)-AR and ß(2)-AR coupled to Gαs exert a proapoptotic action, while ß(2)-AR coupled to Gi exerts an antiapoptotic action. ß1 integrin signaling protects cardiac myocytes against ß-AR-stimulated apoptosis in vitro and in vivo. Interaction of matrix metalloproteinase-2 (MMP-2) with ß1 integrins interferes with the survival signals initiated by ß1 integrins. This paper will discuss background information on ß-AR and integrin signaling and summarize the role of ß1 integrins in ß-AR-stimulated cardiac myocyte apoptosis.