3-hydroxy-3-methylgulutaryl-coenzyme A （HMG-CoA） reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of Cardiovascular diseases. Recent studies suggested that statins, besides lowering cholesterol, may protect vessels by enhancing the activity of endothelial nitric oxide synthase （eNOS）. In the present study, we investigated if simvastatin increases eNOS activity through its phosphorylation in 293 cells （293-eNOS） with stable expression of eNOS. The results showed that incubation of 293-eNOS cells with simvastatin （10 μm/L） for 2 h significantly increased in the activity of eNOS as shown by the conversion of L-arginine to L-citrulline （2889.70±201.51 versus 5630.18＋218.75 pmol/min . mg proteins） （P〈0.01）. Western blotting revealed that simvastatin increased phosphorylation of eNOS at 1177 （ser） and also 495 （thr） but did not affect the overall expression of eNOS or inducible NOS. Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. These results suggest that simvastatin could stimulate,the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.
目的研究过度表达人C-反应蛋白(hCRP)对大鼠血压的影响及其相关机制。方法以重组腺相关病毒为载体,介导hCRP基因(CRP组)或对照基因(GFP组)在大鼠体内表达,观察实验动物血压变化,并以western blot方法检测大鼠主动脉血管紧张素1型受体(AT_1),血管紧张素2型受体(AT_2)的表达。结果CRP组大鼠血压从基因注射后2月开始升高,升高血压的效应在基因导入3月后保持稳定(与对照组相比约升高21 mm Hg)并持续到实验结束。而GFP组血压无明显变化。Western blot结果显示,与对照组相比,CRP组大鼠主动脉AT_1蛋白水平升高,而AT_2蛋白水平降低。结论重组腺相关病毒介导的hCRP过表达可以导致大鼠血压升高,其机制与增加主动脉AT_1表达,降低AT_2表达有关。
