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  • Title: Effects of simvastatin, ezetimibe and simvastatin/ezetimibe on mitochondrial function and leukocyte/endothelial cell interactions in patients with hypercholesterolemia.
    Author: Hernandez-Mijares A, Bañuls C, Rovira-Llopis S, Diaz-Morales N, Escribano-Lopez I, de Pablo C, Alvarez A, Veses S, Rocha M, Victor VM.
    Journal: Atherosclerosis; 2016 Apr; 247():40-7. PubMed ID: 26868507.
    Abstract:
    BACKGROUND: Cholesterol-lowering therapy has been related with several beneficial effects; however, its influence on oxidative stress and endothelial function is not fully elucidated. AIMS: To investigate the effect of simvastatin and ezetimibe on mitochondrial function and leukocyte-endothelium interactions in polymorphonuclear cells of hyperlipidemic patients. METHODS: Thirty-nine hyperlipidemic patients were randomly assigned to one of two groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4-week period. Lipid profile, mitochondrial parameters (oxygen consumption, reactive oxygen species (ROS) and membrane potential), glutathione levels, superoxide dismutase activity, catalase activity and leukocyte/endothelial cell interactions and adhesion molecules -VCAM-1, ICAM-1, E-selectin, were evaluated. RESULTS: An improvement in lipid profile was observed after administration of simvastatin or ezetimibe alone (LDLc: -40.2 vs -19.6%, respectively), though this effect was stronger with the former (p < 0.001), and a further reduction was registered when the two were combined (LDLc: -50.7% vs -56.8%, respectively). In addition to this, simvastatin, ezetimibe and simvastatin + ezetimibe significantly increased oxygen consumption, membrane potential and glutathione content, and decreased levels of ROS, thereby improving mitochondrial function. Furthermore, simvastatin + ezetimibe increased catalase activity. In addition, simvastatin and simvastatin/ezetimibe improved leukocyte/endothelium interactions by decreasing leukocyte rolling and adhesion and increasing leukocyte rolling velocity. Finally, simvastatin, ezetimibe and simvastatin + ezetimibe reduced levels of the adhesion molecule ICAM-1, and ezetimibe + simvastatin significantly decreased levels of E-selectin. CONCLUSION: Co-administration of simvastatin and ezetimibe has an additive cholesterol-lowering effect and beneficial consequences for mitochondrial function and leukocyte/endothelium interactions in leukocytes of hypercholesterolemic patients.
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