Heat Shock Protein 90 Regulates Angiotensin II-induced Vascular Smooth Muscle Cell Hypertrophy through STAT1 Nuclear Translocation and IL-6 Release

Abstract

Heat shock protein 90(Hsp90), one of the most abundant proteins in the eukaryotic cells, is essential for cell survival and its contribution to various cellular processes, including signal transduction has been extensively studied. Hsp90 is also abundant in vascular smooth muscle cells(VSMCs), but its function is largely unknown. In this study, we have investigated the role of Hsp90 in angiotensin II(Ang II)-induced VSMC hypertrophy. An Hsp90- specific inhibitor geldanamycin(GA) abolished Ang II-induced [3H]leucine incorporation levels and decreased the ration of total protein to DNA content in a concentration dependentmanner in VSMCs. In addition, GA significantly suppressed Ang II-induced STAT1 nuclear translocation and IL-6 production. Furthermore, treatment of IL-6-neutralizing antibody decreased Ang II-induced hypertrophy in VSMCs. We also demonstrated that intracellular delivery of Hsp90 significantly restored Ang II-induced hypertrophyin VSMCs. These results suggest Ang II inducesVSMC hypertrophy partly through STAT1 nuclear translocation, IL-6 release and autocrine VSMC activation, and it is regulated by Hsp90