Abstract 19016: ALK2 and ALK3 BMP Type I Receptors Are Required for the Development of Cardiac Hypertrophy

Bone Morphogenetic Proteins (BMP) signaling is required for the development of cardiac hypertrophy. BMP signaling mediates its action via BMP type I and type II receptors. We sought to determine which type I receptors are required for cardiac hypertrophy. We studied BMP signaling in neonatal rat cardiomyocytes (NRCs) stimulated with phenylephrine (PE) or isoproterenol (ISO). In comparison with untreated NRCs, PE (10 μM) and ISO (10 μM) induced hypertrophy, as reflected by increases in cell size (457±50 and 401±35 vs 254±23 μm2, p<0.01) and expression of the gene encoding B-type natriuretic peptide (NPPB; 4.0±1.0 and 3.2±0.8-fold, p<0.01). PE and ISO induced expression of genes specifying BMP2 (6.7±0.5 and 5.6±0.6-fold), BMP7 (4.1±0.4 and 3.6±0.9-fold), and the BMP target gene, Id-1, (3.7±0.1 and 4.2±1.0-fold, p<0.001). PE and ISO also induced phosphorylation of BMP-responsive Smads 1 and 5 and increased activity of a BMP response element-luciferase reporter (14.5±0.8 and 11.9±1.1 vs 5.4±0.4, p<0.01). Incu...