Salidroside inhibits platelet-derived growth factor BB-induced human aortic smooth muscle cell phenotype switching via PDGFR-β/AKT/mTOR/HIF-1α pathway 1

Abstract

Abstract Vascular smooth muscle cell (VSMC) phenotype transformation is the pathological basis of vascular remodeling diseases such as in-stent restenosis after percutaneous coronary intervention. Salidroside has anti-hypoxic and anti-endothelial cell apoptotic effects and inhibits tumor cell proliferation; however, none of the published studies have reported its effect on VSMC phenotype switching to date. In this study, we investigated the effect of salidroside on platelet-derived growth factor BB (PDGF-BB)-induced human aortic smooth muscle cell (HASMC) phenotype switching and explored its pharmacological mechanisms.HASMCs were stimulated with PDGF-BB to establish a cell phenotype switching model and then treated with salidroside. Cell viability was detected using the CCK-8 assay, cell migration was detected by performing the Transwell assay, and F-actin was stained with fluorescently labeled phalloidin. Proliferating cell nuclear antigen, migration-related proteins MMP-9 and fibronectin, phenotype switching markers α-SMA and osteopontin, phosphorylated and non-phosphorylated AKT, mTOR proteins, PTEN, PDGFR-β, and HIF-1α protein were detected through western blotting. Compared with the PDGF-BB indution group, the salidroside treatment group exhibited decreased HASMC proliferation and migration; the expression of the contractile phenotype marker α-SMA increased, and the expression of the secretory phenotype marker osteopontin decreased. Furthermore, phosphorylated AKT, mTOR, PDGFR-β, and HIF-1α protein expression decreased. Salidroside may inhibit phenotype switching of HASMC induced by PDGF-BB through the PDGFR-β/AKT/mTOR/HIF-1α pathway; hence, it may be useful in treating vascular remodeling diseases such as in-stent restenosis after percutaneous coronary intervention.