Protective Effects Of Fluvastatin On Endothelial Cell Injury Induced By Lysophosphatidylcholine

Objective:To observe the protection effects of fluvastatin on human umbilical vein endothelial cells(HUVECs)damaged by lysophosphatidylcholine (LPC),investigate the non-lipid mechanisms of 3-hydroxy-3-methyl-glutaryl coenzyme A(HMG-CoA)reductase inhibitors on antiatherosclerosis and provide a new evidence to statins in clinical application.Methods:The HUVECs were pretreated with fluvastatin at different concentrations for 20 minutes before incubated with lysophosphatidylcholine for 24 hours.The expression of endothelial nitric oxide synthase (eNOS)mRNA and matrix metalloproteinase-9(MMP-9)mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR); the expression of NF-κBp65,ICAM-1 and VCAM-1 protein was detected by immunocytochemistry technique;the cell apoptosis rate was examined by flow cytometry,and the cell viability was measured by MTT.We observed the activity of the superoxide dismutase(SOD),glutathion (GSH)and lactic acid dehydrogenase(LDH),and the changes of the contents of malonaldehyde(MDA)and nitric oxide(NO)in each group by chromatometry.Results:1.Lysophosphatidylcholine could significantly upregulate the expression of MMP-9 mRNA and the protein of NF-κBp65,ICAM-1, VCAM-1,inhibit the expression of eNOS mRNA,reduce the activity of SOD,GSH,the contents of NO and the cell viability,and increase the activity of LDH,the content of MDA and the cell apoptosis rate.2. Fluvastatin could attenuate the above-mentioned effects in a dosedependent manner.3.N(omega)-nitro-L-arginine methyl ester,the inhibitor of nitric oxide synthase,could reduce the activity of nitric oxide synthase and decrease the synthesis of NO,which could abolish the protection of fluvastain partly.Conclusion:1.Lysophosphatidylcholine could lead to functional disorder of endothelial cells by inducing oxidative stress and inflammatory reaction in vascular endothelial cells.2.Fluvastain could inhibit oxidative stress induced by lysophosphatidylcholine in a dose-dependent manner through increasing the synthesis of NO,which could protect endothelial cells against oxygen free radical.3.Fluvastatin could inhibit the activity of NF-κB by increasing the synthesis of NO,which could decrease the expression of ICAM-1,VCAM-1,and MMP-9,and inhibit inflammatory reaction and stabilize atheromatous plaque.4.The protective effects of fluvastain on HUVECs might be related to other pathways except increasing the synthesis of NO.