βAr-cAMP Signaling Pathways Inhibit The Proliferation Of Vascular Smooth Muscle Cell Through Increase The Expression Of Mfn2

Objective To investigate the effect ofβadrenergic receptor(AR)- adenylate cyclase(AC) cyclic adenosine monophosphate(cAMP) signaling pathway on the proliferation of vascular smooth muscle cells(VSMCs) and the expression of mitofusin 2(Mfn2).Method VSMCs were cultured in vitro and were stimulated by different concentration of isoprenaline(ISO) or forskolin(FSK). The effect of ISO on the proliferation of VSMC was observed by cell counting and WST-1 assay. Western blot was used to explore the expression of Mfn2, p-Raf-1 and p-ERK1/2 between the two different intervention methods, and the expression of Mfn2 and p-ERK1/2 after small interfering RNA(siRNA)-mediated silencing of Mfn2 in VSCMs.Result ISO inhibited the proliferation of VSMC in a dose-dependent manner. There were similar effect on the expression of Mfn2, p-Raf-1 and p-ERK1/2 between the groups treated by different concentration of ISO and FSK. The result showed that both of ISO and FSK increased the expression of Mfn2 in a dose-dependent manner and decreased the expression of p-Raf-1 and p-ERK1/2 in a dose-dependent manner. Mfn2 silencing with Mfn2 siRNA protects VSMC against the inhibition of VSMC proliferation induced byβAR activity.Conclusion 1,βAR activity could inhibit VSMC proliferation. 2,βAR-AC-cAMP signaling pathway is an upstream regulation pathway of Mfn2.