The Study On The Effect Of Mfn2-1A On Apoptosis Of VSMC

Objective To investigate the effect of Mfn2-1A on inducing the apoptosis of VSMCand underlying mechanism.Methods The fragment sequence of Mfn2-1A contains the p21rassignature motif andATP/GTP-binding site motif. VSMCs separated from spontaneously hypertensive ratwere transfected with adenovirus-mediated1A (Adv-Mfn2-1A) or adenovirus-mediatedMfn2(Adv-Mfn2), and compared with Control and LacZ respectively. The effect ofMfn2-1A on the apoptosis of VSMC was determined by Cell Death ELISA. The flowcytometry analysis was used to analyze the percentage of VSMCs undergoing apoptosis.The protein expression of p-Akt was determined by western blot.Results VSMCs which were infected with Adv-Mfn2-1A expressed Mfn2protein.Compared with control group, VSMCs infected with Adv-Mfn2-1A or Adv-Mfn2expressed more Mfn2protein. Cell Death ELISA showed that the apoptosis ofAdv-Mfn2-1A infected cells were more severe than that of Adv-Mfn2infected cells after72h(P＜0.05). The flow cytometry analysis demonstrated that both Mfn2-1A and Mfn2could promote the apoptosis of VSMCs compared to Control and LacZ(P＜0.05). Alsothe percentage of apoptosis in VSMCs infected with Mfn2-1A was greater than that infected with Mfn2. Western blot showed that overexpression of Mfn2-1A leaded todownregulation of P-Akt, and this downregulation effect was more significant inMfn2-1A transfection group than that of Mfn2group(P＜0.05).Conclusions Mfn2-1A can induce apoptosis of vascular smooth muscle cells via theRas-Akt signaling pathway, and the effect is much greater than that of Mfn2gene.