The Effects Of Simvastatin On Expression Of T-PA,PAI-1,No And NOS In Cultured Human Endothelial Cells During Hypoxia-reoxygenation

Endothelial dysfunction is an early marker of atherosclerosis and is often defined as the impaired release or activity of endothelium-derived relaxing factor (EDRF).clinical analysis shows that statins can decrease PAI-1 in coronary atherosclerotic heart disease.Statins are widely used for the treatment of hyperlipidemia and also for the prevention of coronary artery disease.Although the mechanism by which HMG CoA reductase inhibitors restore endothelial function has been almost exclusively attributed to the lowering of serum cholesterol levels.recent study shows that HMG CoA reductase inhibitors can be beneficial in atherosclerosis is through their direct effects on the vascular wall-----non-lipid mechanisms of statins on anti-atherosclerosis .However little is known whether HMG CoA reductase inhibitors can restore endothelial function during one of the most common and predictable forms of hypoxia and reoxygenation injury which offen occurs during angina,reperfusion therapy to acute myocardial infaction and cardiopulmonary bypass.Thus the purpose of this study is to determine secretion of t-PA,PAI-1,NO ,the activity of NOS and the nitric oxide synthase expression in cultured human endothelial cells during hypoxia–reoxygenation, and access the effects of simivastatin on them.ECV304 cells were cultured without or with simvastatin at various concentrations and 10.0μmol/L simvastatin plus 0.2 mmol/L mevalonate for 24 hours, before and after they were stimulated by hypoxia-reoxygenation respectively. The concentration of t-PA,PAI-1,NO and the activity of NOS in the supernatants was determined by ELISA,Nitrate reductase assay, and the activity of NOS was measured by Chemical colorimetric assay. RT-PCR and Western blots were used to detect the iNOS,eNOSmRNA...