Homocysteine-induced apoptosis of endothelial cells and roles of caspase3 / 上海第二医科大学学报

ABSTRACT

Objective To investigate whether homocysteine(Hcy) induces apoptosis of endothelial cells via a pathway involving caspases3 and whether simvastatin antagonizes the proapoptotic effects of Hcy by regulating c-IAP. Methods Human umbilical vein endothelial cells(HUVEC) were treated with Hcy,with or without simvastatin,for 24 h.Cell apoptosis was evaluated by Annexin V staining and flow cytometery,as well as TUNEL.The mRNA and protein levels of caspase3,c-IAP-1 and c-IAP-2 were analyzed by RT-PCR and Western blot,respectively. Results Treatment with both low(0.5 mmol/L) and high(3.0 mmol/L) concentrations of Hcy-induced HUVEC apoptosis was accompanied by an increased level of caspase3 expression and activation,together with decreased c-IAP-1 and c-IAP-2 level.Simvastatin upregulated c-IAP-1 and c-IAP-2 expression while attenuated Hcy-induced apoptosis and caspase3 activation. Conclusion Hcy may induce HUVEC apoptosis via a pathway involving caspase3,which can be partially antagonized by simvastatin,possibly through upregulated c-IAP-1 and c-IAP-2 expression.