Paeonol inhibits ox-LDL-induced apoptosis,inflammation,and oxidative stress of mouse vascular endothelial cells by regulating the miR-152-3p/ASPH axis in atherosclerosis
Objective The study was to uncover the action of paeonol in the progression of ox-LDL-stimulated vascular endothelial cells(VECs)via modulating microRNA(miR)-152-3p/aspartate-β-hydroxylase(ASPH)axis.Methods First,mouse VECs were treated with different concentrations of ox-LDL(0,25,50,100 μg·mL-1),and 100 μg·mL-1 was selected for further experiments.Then,VECs were treated with different doses of paeonol(30,60,120 μmol·L-1)or simvastatin(30 μmol·L-1).Then,determination of cell viability and apoptosis was via adopting cell counting kit-8(CCK-8)and flow cytometry.Additionally,analysis of interleukin(IL)-1β and IL-6 was conducted,and test of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and malondialdehyde(MDA)contents was via adopting relevant kits.Furthermore,examination of miR-152-3p and ASPH was performed.Forecast of the interaction of miR-152-3p with ASPH was via starBase with verification.Results Ox-LDL(100 μg·mL-1)significantly inhibited the viability of VECs and promoted apoptosis,inflammatory response and oxidative damage.Paeonol treatment increased cell viability and inhibited ox-LDL-induced apoptosis in a dose-dependent manner.Moreover,paeonol reduced the levels of IL-1β and IL-6 induced by ox-LDL in a dose-dependent manner,and attenuated the promoting effects of ox-LDL on ROS,MDA and LDH content.In addition,the inhibitory effect of ox-LDL on miR-152-3p expression and the promotion effect on ASPH expression were also reversed by paeonol,and paeonol(120 μmol·L-1)had the best effect.Therefore,paeonol(120 μmol·L-1)was selected for subsequent transfection experiments.Up-regulation of miR-152-3p or down-regulation of ASPH could further promote the protective effect of paeonol on the growth of VECs,and miR-152-3p targeted and negatively regulated ASPH expression.Conclusion Paeonol attenuates the impact of ox-LDL on the growth of VECs in mice via controlling miR-152-3p/ASPH axis,offering a theoretical basis for AS cure.