Protective Effects And Mechanisms Of Lovastatin On Vascular Endothelium Injuries Caused By Lysophosphatidylcholine

AIM To investigate the protective effects and mechanisms of lovastatin on vascular endothelium injuries induced by lysophosphatidyl choline(LPC).METHODS Both isolated rat thoracic rings and cultured human endothelial cells were used.(1) The isolated rat thoracic rings were divided into five groups:①Normal control group;②LPC-injured group: vascular rings were incubated with LPC(4 mg/L) for 15 min;③～⑤Lovastatin(Lov)-treated group:vascular rings were pretreated with lovastatin(0.025,0.05,0.1μmol/L) before LPC incubation.The vascular endothelial-dependent and -independent relaxation were examined. Forthermore,the content of the metabolic production of the lipid peroxidation,malondialdehyde(MDA) in vascular tissue were also measured.(2) In cultured human umbilical vein endothelial cells (HUVECs),the experiment groups were devived as follows:①Control group,②Lov group(0.1μmol/L),③LPC group(4 mg/L),④～⑥LPC (4 mg/L) +Lov(0.025μmol/L,0.05μmol/L,0.1μmol/L) group.The endothelial cells vitality,eNOS activity and NO content were determined. Moreover,the ROS production and the activation of the NF-κB in HUVECs were also observed.RESULTS(1) In isolated rat thoracic rings:LPC significantly decreased the endothelial-dependent relaxation and increased the content of MDA in vascular tissue.Pre-incubation of the vascular rings with lovastatin(0.025,0.05,0.1μmol/L) concentration-dependently improved endothelial-dependent relaxation injuried by LPC and decreased content of MDA increased by LPC.(2) LPC signifcicantly inhibited activity of eNOS and vitality of endothelial cells,decreased the content of NO,increased the ROS production and NF-κB activation. Lovastatin markedly increased the levels of NO,reduce the production of ROS and inhibited the activation of NF-κB.CONCLUSION LPC could directly inhibit endothelial-dependent relaxation induced by ACh,lovastatin may protect the endothelial cells from injury caused by LPC.The protective effects of lovastatin may be related to its antioxidant and antiinflammatory properties.