tMfn2 gene transfer promotes vascular smooth-muscle cells apoptosis via activation of the mitochondrial cell death pathway / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of tMfn2 gene transfer on promoting the apoptosis of vascular smooth-muscle cells (VSMCs).</p><p><b>METHODS</b>VSMCs were infected by adenovirus-mediated tMfn2 (Adv-tMfn2) or adenovirus-mediated Mfn2 (Adv-Mfn2). FACS analysis, cell death ELISA and TUNEL staining were used to investigate the role of tMfn2 and Adv-Mfn2 gene transfer on VSMCs apoptosis. Western blot was used to analyze the protein expression of p-Akt, Bcl-2, Bax and cleaved caspase-9.</p><p><b>RESULTS</b>FACS and ELISA results showed that tMfn2 was superior to Mfn2 in promoting VSMCs apoptosis and tMfn2 gene transfer induced VSMCs apoptosis in a time-dependent manner (P < 0.01). TUNEL staining evidenced that there were more positive-apoptotic VSMCs in tMfn2 group than that in Mfn2 group (P < 0.01). The protein expressions of phosphorylated Akt and Bcl-2 were significantly decreased, whereas Bax and cleaved caspase-9 protein expressions were significantly upregulated in tMfn2-transfected VSMCs.</p><p><b>CONCLUSIONS</b>tMfn2 transfer promoted apoptosis of VSMCs in a time dependent manner via the PI3K-Akt signaling pathway and mitochondrial apoptotic pathway.</p>