Salidroside Inhibits Platelet-Derived Growth Factor Bb-Induced Human Aortic Smooth Muscle Cell Phenotype Switching Via Pdgfr-Β/Akt/Mtor/Hif-1α Pathway1

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.

Note:
Funding declaration: The present study was supported by the Foundation of Key Scientific Research Projects of Higher Education Institutions in Henan Province (grant nos. 18A320005 and 19A360032). Henan Province medical science and technology joint construction project project directory(grant nos. LHGJ20221049).

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that might affect the research reported in this paper.

Keywords: Salidroside, phenotype switching, human aortic smooth muscle cell, PDGFR-β/AKT/mTOR/HIF-1α pathway, vascular smooth muscle cell, platelet-derived growth factor BB