Simvastatin suppresses homocysteine-induced apoptosis in endothelial cells: roles of caspase-3, cIAP-1 and cIAP-2.

The present study addresses how homocysteine (Hcy) induces endothelial apoptosis and how simvastatin antagonizes these pro-apoptotic effects of Hcy.Human umbilical vein endothelial cells (HUVECs) were treated with Hcy for 24 h, in the presence or absence of simvastatin. Cell apoptosis was evaluated by Annexin V staining and flow cytometry, as well as transferase-mediated dUTP-biotin nick end labeling (TUNEL). The mRNA and protein levels of caspase-3, cellular inhibitor of apoptosis (cIAP)-1 and -2 were analyzed by real-time polymerase chain reaction (RT-PCR) and western blotting, respectively.Treatment with both low (0.05 mmol l(-1)) and high (0.3 mmol l(-1)) concentrations of Hcy induced apoptosis in HUVECs which was accompanied by an increased level of caspase-3 expression and activation, together with decreased cIAP-1 and cIAP-2 levels. Conversely, simvastatin upregulated c-IAP1 and c-IAP2 expression, while attenuating Hcy-induced apoptosis and caspase-3 activation. Hcy may induce HUVEC apoptosis through a pathway involving caspase-3. This induction can be partially antagonized by simvastatin, possibly through upregulation of cIAP-1 and cIAP-2.