Impact of PM2.5 on vascular smooth muscle cell activation via endothelial cells and protective effect of oleanolic acid nanoparticles
Objective To understand the effect of PM2.5 on vascular smooth muscle cell(HVSMCs)activation via vascular endothelial cells(VECs)and protective effect of oleanolic acid nanoparticles(OA-NP).Method Two co-culture models were established to explore the indirect effect of PM2.5 to HVSMCs:one using conditioned medium from PM2.5-exposed EA.hy926 cells with HVSMCs,and the other utilizing a Transwell chamber for co-culturing PM2.5-exposed EA.hy926 cells with HVSMCs.CCK-8 assay,EdU-488 assay,scratch assay and Transwell assay assessed the proliferation and migration of HVSMCs.CCK-8 assay was employed to assess the toxicity of OA-NP to EA.hy926 cells,aiming to determine the optimal drug concentration.EA.hy 926 cells were divided into the blank group(PBS),PM2.5 group(25 μg/ml,model group),the reactive oxygen species(ROS)inhibitor NAC group(10 μmol/L,positive control group),and low,medium,and high concentrations(2,4,8 μmol/L)of OA-NP group.Then co-cultured with HVSMCs and the same assays were performed to study the protective effect of OA-NP.Flow cytometry was used to detect the production of ROS within EA.hy926 cells.Result In both co-culture models,compared to the blank group,PM2.5-exposed EA.hy926 cells or its conditioned medium significantly promoted the proliferation and migration of HVSMCs(P＜0.01).Compared to the model group,pre-treatment with NAC or OA-NP both significantly inhibited ROS production in PM2.5-exposed EA.hy926 cells(P＜0.01),as well as the proliferation and migration of HVSMCs co-cultured(P＜0.01).Conclusion PM2.5 can induce the proliferation and migration of HVSMCs indirectly by inducing oxidative stress in VECs.The application of OA-NP can effectively inhibit PM2.5-induced oxidative stress in VECs,protecting HVSMCs and suggests a potential protective role against PM25 cardiovascular toxicity.
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