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.