The Role Of Caveolin-1/STAT3 In Autophagy And Proliferation Of Vascular Endothelial Cells Induced By Angiotensin Ⅱ

To investigate whether caveolin-1 mediates the autophagy and proliferation of endothelial cells induced by angiotensinⅡvia STAT3.Methods:Taking human umbilical vein endothelial cell beads(HUVECs)as the research object,HUVECs were treated with different concentrations of AngⅡ(1n M,10 n M,100 n M)for 24 hours,and the proliferation rate of HUVECs was detected by CCK-8.Cytometry measures the cell proliferation cycle.RT-PCR was used to detect the expression of Cav-1 and STAT3 m RNA in the cells;Western Blot was used to detect the expression of Cav-1,STAT3,ph-STAT3,PCNA and ki-67 proteins.The Cav-1 inhibitor β-cyclodextrin(20μM)treating HUVECs for 1h,or 24 h after infection with lentivirus containing Cav-1 interference sequence,100 n M AngⅡ was given for 24 h,and Western Blot was used to detect the expression of Cav-1,STAT3 and ph-STAT3 proteins.Cells were infected with lentivirus containing STAT3 interference sequence for 24 h,and then treated with 100 n M AngⅡfor 24 h.Western Blot was used to detect the expression of Cav-1,STAT3,ph-STAT3,LC3 and p62 protein.Results: Results showed that the cell survival rate of the AngⅡgroup was increased compared with the control group,and the cell survival rate of the inhibitor β-cyclodextrin group was decreased compared with the AngⅡ group.Proliferation marker protein PCNA,ki-67 protein expression levels were down-regulated,and both of S phase and G2/M cells were decreased inβ-cyclodextrin group,but G1 phase was increased.AngⅡup-regulated the expression of Cav-1 m RNA in a concentration-dependent manner.Similarly,AngⅡ also up-regulated the expression of ph-STAT3 in a dose-effect relationship,but had no obvious effect on the expression of STAT3 m RNA and its protein.After silencing Cav-1,compared with the AngⅡ+NC group,the AngⅡ+sh Cav-1 group had down-regulated ph-STAT3 protein expression.After silencing STAT3,compared with the Control group,the expression of autophagy marker LC3 in the AngⅡ group was up-regulated,and the expression of p62 protein was down-regulated,compared with the AngⅡ+NC group,In the group of AngⅡ+sh STAT3,the expression of Cav-1 protein did not change significantly,but the expression of autophagy marker protein LC3 was down-regulated,and the expression of P62 protein was up-regulated.Conclusion: Cav-1 mediates the proliferation of human umbilical vein endothelial cells induced by AngⅡthrough promoting autophagy via activation of STAT3 signal.