Angiotensin II -induced overexpression of Sirtuin-1 contributes to enhanced expression of Gi α proteins and hyperproliferation of vascular smooth muscle cells

Am J Physiol Heart Circ Physiol. 2021 Jul 16. doi: 10.1152/ajpheart.00898.2020. Online ahead of print.ABSTRACTAngiotensin II (Ang II) plays an important role in the regulation of various physiological functions including proliferation, hypertrophy of vascular smooth muscle cells (VSMC) through the overexpression of Giα proteins. Sirtuin1 (Sirt1), a class III histone deacetylase and epigenetic regulator is implicated in a wide range of cellular functions, including migration and growth of VSMC as well as in Ang II-induced hypertension. The present study was undertaken to examine the role of Sirt1 in Ang II-induced overexpression of Giα proteins and hyperproliferation of aortic VSMC. We show that Ang II treatment of VSMC increased the expression of Sirt1 which was attenuated by AT1 and AT2 receptor antagonists, losartan and PD123319 respectively. In addition, knockdown of Sirt1 by siRNA attenuated Ang II-induced overexpression of Giα-2 and Giα-3 proteins, hyperproliferation of VSMC as well as the overexpression of cell cycle proteins, cyclin D1, Cdk4 and phosphorylated retinoblastoma proteins. Furthermore, Ang II-induced increased levels of superoxide anion (O2-) and NADPH oxidase activity and increased phosphorylation of ERK1/2 and AKT that are implicated in enhanced expression of Giα proteins and hyperproliferation of VSMC were also attenuated to control levels by silencing of Sirt1. In addition, depletion of Sirt1 by siRNA also attenuated Ang II-induced enhanced phospho...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research