Key result
Fenofibrate ameliorated endothelium-dependent vasodilation and relieved high glucose-induced endothelial dysfunction in diabetic mice, possibly via activation of eNOS and AMPK phosphorylation.
Why the study?
Fenofibrate reduces cardiovascular events in diabetes, but whether it ameliorates endothelium-dependent vasodilation and relieves high glucose-induced endothelial dysfunction via eNOS and AMPK phosphorylation required investigation.
Does fenofibrate improve vascular endothelial function in diabetic mice?
Does fenofibrate improve vascular endothelial function in diabetic mice?
Fenofibrate improves vascular endothelial function in diabetic mice, likely via activation of eNOS and AMPK phosphorylation.
Hypothesis-generating for fenofibrate in diabetic endothelial dysfunction; human trials needed before any clinical consideration.
Microvascular and macrovascular complications are major causes of disability and death in diabetic patients. High levels of blood glucose sabotage the integrity of blood vessels and induce endothelial dysfunction. Fenofibrate is an agonist of peroxisome proliferator-activated receptor α and can reduce the incidence of cardiovascular events in diabetic patients. 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 (O 2 − ) 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 O 2 - in diabetic mouse aortae. In-vitro, fenofibrate treatment improved the impaired function of MAECs, increased nitric oxide production, and decreased the O 2 - level, as well as activated eNOS and AMPK phosphorylation in cultured MAECs by high glucose. Fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction, which was possibly related to the activation of eNOS and AMPK phosphorylation.
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Xin et al. (2019) studied Diabetes. Fenofibrate was evaluated on Endothelium-dependent vasodilation and endothelial function. Fenofibrate ameliorated endothelium-dependent vasodilation and relieved high glucose-induced endothelial dysfunction in diabetic mice, possibly via activation of eNOS and AMPK phosphorylation.
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