HB-EGF, Transactivation, and Cardiac Hypertrophy

SUMMARYTransactivation of epidermal growth factor receptor (EGFR) family ligands by G protein coupled receptor (GPCR) agonist plays important roles in many physiologic activities. In the heart, heparin-binding EGF-like growth factor (HB-EGF), which is one of the EGF family ligands, is an indispensable molecule for cardiac cell metabolism. Membrane-anchored HB-EGF is released by GPCR agonist stimulation and moves signals leading to hypertrophy. Amelioration of this signal transduction by HB-EGF genome deletion causes severe heart dysfunction, indicating the important role of HB-EGF in the heart. Cleavage of HB-EGF was mediated by activation of membrane-anchored metalloprotease. Inhibitor of metalloprotease prevents activation of HB-EGF andattenuates hypertrophic response of cardiomyocytes by GPCR agonists such as angiotensin II or catecholamine. These data strongly suggest that HB-EGF is involved in cardiac development and metabolism. The physiologicand clinical roles of EGF family ligands in the heart are reviewed