The Regulation of MiR-143/145 on Akt Signaling during VSMC Phenotype Switching in Exercise-induced Hypertensive Arteries / 中国运动医学杂志

ABSTRACT

Objective To explore the effect of exercise on vascular smooth muscle cell(VSMC) phenotype switching in hypertensive arteries and to figure out the regulatory mechanisms of mircroRNA (miR)-143/145 on Akt signaling during the process.Methods Three-month old(Wistar Kyoto rats) WKY and (spontaneously hypertensive rats) SHR were divided into 4 groupsWKY-C,SHR-C,WKY-E,and SHR-E,which were subjected to 8wk moderate treadmill training (E) or sedentary as control (C) with blood pressure being monitored.After the last bout of exercise,mesenteric arteries were isolated to determine VSMC phenotypic marker,miR143/145 expression and Akt phosphorylation.In transfection experiment in vitro,miR-145 mimic and miR-145 inhibitor were transfected into cultured VSMC,and given immunofluorescent staining using α-actin to detect the cell morphology.VSMC phenotype marker,Akt phosphorylation,and mRNA expressions of the insulin-like growth factor Ⅰ receptor (IGF-IR),Insulin receptor substrate 1 antibody(IRS-1),and p70S6K were determined.Results The blood pressure of SHR-E reduced significantly compared with that of SHR-C(P＜0.05),and the arterial thicknessof SHR-E decreased significantly (P＜0.05).The VSMC contractile marker calponin in SHR-E increased significantly when compared with SHR-C(P＜0.05),while the proliferative marker osteoppontin (OPN) in SHR-E reduced significantly than that in SHR-C(P＜0.05).The miR-145 of SHR-E was significantly enhanced(P＜0.05),while there was no significant difference in the miR-143.The Akt of SHR-E was activated more significantly than SHR-C(P＜0.05).The miR-145 overexpression by transfecting miR-145 mimic into VSMC increased α-actin significantly(P＜0.05),while miR-145 inhibitor made α-actin a decrease.Akt activation was significantly inhibited by miR-145 mimic and enhanced by miR-145 inhibitor(P＜0.05).The miR-145 significantly inhibited IRS-1 and IGF-1R mRNA(P＜ 0.05),but the targeting effects were not significant on p70S6K mRNA.Conclusions Exercise ameliorates the high blood pressure and remodels arterioles,which may rely on its regulatory role on VSMC switching from proliferative to contractile phenotype,and miR-145 is involved in this process.However,the Akt activation is not caused by the overexpression of miR-145,but through other means to promote the above VSMC switching.