Heparin and Heparan Sulfate Block Angiotensin IIInduced Hypertrophy in Cultured Neonatal Rat Cardiomyocytes

Background Heparan sulfate, one of the primary components of extracellular matrix, is a potent antigrowth factor in certain types of cells. To elucidate a possible role of endogenous heparin-like molecules in regulating cardiomyocyte hypertrophy, we investigated the effects of heparin and heparan sulfate on angiotensin (Ang) II–induced hypertrophy in cultured neonatal rat cardiomyocytes. Methods and Results Competitive [3H]heparin binding assay showed that cardiomyocytes had specific binding sites for heparin. In situ [3H]heparin binding assay demonstrated that heparin, which rapidly bound to the cardiomyocyte surface, was subsequently accumulated around the nuclei, suggesting that heparin might work in the nucleus. Cotreatment with heparin (20 μg/mL) completely inhibited increased cell surface area by Ang II (10−6 mol/L). Increased [3H]leucine incorporation by Ang II was reduced by heparin dose-dependently. The inhibitory effect of heparin on Ang II–induced cardiomyocyte hypertrophy also was confirmed by...