Curcumin-mediated Photodynamic Therapy Regulates The Effects Of Vascular Smooth Muscle Cells By Promoting Autophagy In Atherosclerosis

Background: Atherosclerosis(AS)is an important inducer of cardiovascular and cerebrovascular diseases at present,and vascular smooth muscle cells(VSMC)is an important component of vascular wall.Therefore,more and more scholars have focused on vascular smooth muscle cells as the target for the treatment of atherosclerosis.Objective: This study was designed to observe the specific effects of curcumin-mediated photodynamic therapy(CUR-PDT)on oxidized low-density lipoprotein(ox-LDL)-treated(VSMC)and explore the basic cellular mechanisms involved.Methods: In this study,the MOVAS and A7r5 cell lines were used for parallel experiments.VSMC viability was evaluated by CCK-8 assay.The production of ROS was measured with DCFH-DA.VSMCs were treated with ox-LDL to establish a model of atherosclerosis in vitro.The autophagy level and the expression of proteins related to phenotypic transformation were detected by western blotting.The migration ability of the cells was detected by using transwell assay.The presence of intracellular lipid droplets was detected by Oil Red O staining.Result: CUR-PDT decreased the cell activity of VSMC in a dose-dependent manner and promoted the production of ROS compared with other groups.The degree of lipid droplets increased in a concentration-dependent manner in VSMC treated with ox-LDL to induce AS model in vitro.Compared with control group,the presence of ox-LDL can stimulate the transformation of VSMC to synthetic phenotype,manifested that the expression of contractile phenotypic marker α-SMA and SM22-α were significantly decreased,while the expression of synthetic phenotypic marker OPN was significantly increased.And ox-LDL could enhance the migration ability and lipid droplet aggregation of VSMC.At the same time,ox-LDL treatment impeded the autophagy level of VSMC compared with control group,showing that the expression of autophagy-related proteins Beclin-1 and LC3B-Ⅱ were significantly reduced and the degradation of p62 was reduced.Compared with ox-LDL group,CUR-PDT could significantly up-regulate the expression of α-SMA and SM22-α,and significantly down-regulate the expression of OPN,and inhibit the migration of VSMC and lipid droplet aggregation.In addition,CUR-PDT increased the expression of Beclin-1 and LC3B-Ⅱ as well as the degradation of p62 compared with ox-LDL group.After pretreatment with the autophagy inhibitor 3-methyladenine(3-MA),the effects of CUR-PDT on phenotype transformation,migration,and lipid droplet aggregation in ox-LDL-treated VSMC were reversed.Conclusion: CUR-PDT can inhibit the phenotypic transformation,migration and foaming of ox-LDL-treated VSMC by inducing autophagy.