Abstract
In contrast to statins, ezetimibe belongs to a new class of cholesterol-lowering agent not known to mediate pleiotropic effects. Here we investigate whether ezetimibe or simvastatin can help recover blood flow and reduce tissue damage after hindlimb ischemia surgery in diabetic mice. Diabetic mice were created by intraperitoneal streptozotocin injection in male FVB/NJ mice. All diabetic mice were subsequently divided into three groups: diabetic control, diabetic with simvastatin (0.2 mg/kg), and diabetic with ezetimibe (0.1 mg/kg). All experimental mice received hindlimb ischemia surgery after 2 weeks of drug treatment. Circulating endothelial progenitor cell number was determined by flow cytometry (Sca-1+/C-kit+/Flk-1+) in peripheral blood. In comparison to the mice in the diabetic control group (n = 6), wild-type mice (n = 6) and diabetic mice that received simvastatin (n = 6) had significantly increased ischemic/nonischemic limb blood perfusion ratio, higher capillary density (P < .05, respectively), and reduced ischemic limb damage (diabetic control, 80%; diabetic with simvastatin, 40%; diabetic with ezetimibe, 80%). However, these proangiogenic effects were not observed in diabetic mice that had been treated with ezetimibe...Continue Reading
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