同型半胱氨酸诱导内皮细胞凋亡caspase3途径作用的机制

目的了解同型半胱氨酸(Hcy)是否通过caspase途径诱导内皮细胞凋亡,以及辛伐他汀是否可以通过调节c-IAP行使其拮抗效应。方法Hcy、辛伐他汀或两者联合处理人脐静脉内皮细胞(HUVEC)24 h后,采用Annexin V染色加流式细胞术及TUNEL观察细胞凋亡状态;RT-PCR和蛋白质印迹技术检测caspase3、c-IAP-1和c-IAP-2的mRNA和蛋白质水平。结果0.5 mmol/L和3 mmol/L的Hcy均导致HUVEC凋亡,Hcy浓度高时凋亡细胞数较高,并伴有caspase3表达和活化增强;c-IAP-1、c-IAP-2的mRNA和蛋白质水平降低;辛伐他汀可以上调c-IAP-1和c-IAP-2的表达。结论Hcy诱导HUVEC凋亡作用可能涉及caspase3相关途径;辛伐他汀可促进c-IAP系统的表达,从而部分拮抗Hcy的作用。

Homocysteine-induced apoptosis of endothelial cells and roles of caspase3

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.