Irisin/PPARá Mediates the Proliferation and Apoptosis of Ascular Smooth Muscle Cells through Activation of the HO-1

Objective: This study aimed to investigate the function and mechanism that Irisin/ PPARαsignaling pathway mediates the balance between proliferation and apoptosis in vascular smooth muscle cells (VSMCs). Methods: : VSMCs were transfected with FNDC5 overexpression and silencing lentiviral vectors to increase or inhibit Irisin production; the cells were randomly divided into 7 groups:the control group (control), overexpressing empty lentiviral vector group (MOCK1), FNDC5 overexpressing group (FNDC5), overexpressing empty vector with PPARα inhibitor group (MOCK1 + GW6471), FNDC5 overexpressing with PPARα inhibitor group (FNDC5 + GW6471), silencing empty lentiviral vector group (MOCK2) and FNDC5 silencing group (sh- FNDC5).The expression levels of FNDC5, PPARα, HO-1, Bax, and Bcl-2 in each group were detected by Real-time PCR and Western blot, respectively. The Proliferation and Apoptosis of VSMCs were conducted by using flow cytometry. The gell proliferation rate was detected through CCK8 assay. Results: : Compared with the control group or MOCK1 group, the expressions of FNDC5, PPARα, HO-1 and Bax，and the Bax/Bcl-2 ratio，increased significantly in FNDC5 and FNDC5+GW6471 group(P < 0.05) , while the expression of Bcl-2 decreased significantly in MOCK+GW6471 group (P < 0.05). Conclusions: : The HO-1 induced by Irisin/PPARα,inhibited the proliferation of VSMCs through repressing DNA synthesis ,and regulated expressions of the important functional molecules in the cell apoptosis pathway to promote the cell death，therefore, we drew a conclusion that Irisin/PPARα mediates the the balance between proliferation and apoptosis of ascular smooth muscle cells through activing the HO-1.