Statins protect diabetic myocardial microvascular endothelial cells from injury

Abstract

To study the protective effect and mechanism of statins on myocardial microvascular endothelial cells injury in diabetic rats. The rats were administrated with atorvastatin (10 mg/kg/day), rosuvastatin (5 mg/kg/day), or placebo for 1 week. The expression of small GTP-binding protein dissociation stimulator (SmgGDS) was analyzed using western blot. The expression of SmgGDS was also analyzed in cultured rat cardiac microvascular endothelial cells using western blot. The cells were divided into normal glucose group, hyper glucose group, and atorvastatin-treated group. The superoxide dismutase (DHE) staining was used to detect the oxidative stress in the rat cardiac microvascular endothelial cells. The expression of SmgGDS was detected using TUNEL staining after knockout of Akt1 and β1-integrin in cardiac microvascular endothelial cells. The followings were the significant findings of this study: (1) SmgGDS was expressed in aorta endothelium of diabetic rats and cardiac microvascular endothelial cells cultured with high glucose, (2) high glucose increased the production of ROS, the activity of NADPH, and the rate of apoptosis in cardiac microvascular endothelial cells, but after atorvastatin pretreatment, the production of ROS, the activity of NADPH, and the rate of apoptosis in cardiac microvascular endothelial cells decreased, (3) the expression of SmgGDS decreased and the oxidative stress increased after knockdown of Akt1 or β1-integrin. Statins can protect diabetic microvascular endothelial cells from oxidative stress and apoptosis by upregulating SmgGDS partly through β1-integrin/Akt1 pathway.