Fenofibrate improves vascular endothelial function in diabetic mice

This study tested the hypothesis that fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction via activating endothelial nitric oxide synthase (eNOS) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. A streptozotocin (STZ)-induced diabetic model was established by intraperitoneal injection of STZ (dissolved in sodium citrate buffer) at a dose of 60 mg/kg for 5 consecutive days. Mice were administered fenofibrate (100 mg/kg/d, i.g.) for 14 days. The endothelial function of extracted mouse aortae was examined by evaluating acetylcholine induced endothelium-dependent relaxation combined with phenylephrine-induced vasoconstriction and sodium nitroprusside-induced endothelium-independent relaxation. Superoxide onion (O2−) was determined using dihydroethidium staining of aortae. Functions of mouse aortic endothelial cells (MAECs) were assessed, and expression levels of eNOS and AMPK were determined by Western blotting. Fenofibrate ameliorated the impaired endothelium-dependent relaxation in diabetic mice and decreased the level of intracellular O2- in diabetic mouse aortae. In-vitro, fenofibrate treatment improved the impaired function of MAECs, increased nitric oxide production, and decreased the O2- level, as well as activated eNOS and AMPK phosphorylation in cultured MAECs by high glucose. Fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic m...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research