辛伐他汀、依折麦布及辛伐他汀/依折麦布对高胆固醇血症患者线粒体功能及白细胞/内皮细胞相互作用的影响。

Effects of simvastatin, ezetimibe and simvastatin/ezetimibe on mitochondrial function and leukocyte/endothelial cell interactions in patients with hypercholesterolemia.

作者信息

Hernandez-Mijares Antonio, Bañuls Celia, Rovira-Llopis Susana, Diaz-Morales Noelia, Escribano-Lopez Irene, de Pablo Carmen, Alvarez Angeles, Veses Silvia, Rocha Milagros, Victor Victor M

机构信息

Service of Endocrinology, University Hospital Dr. Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain.

出版信息

Atherosclerosis. 2016 Apr;247:40-7. doi: 10.1016/j.atherosclerosis.2016.01.044. Epub 2016 Feb 4.

DOI:10.1016/j.atherosclerosis.2016.01.044

PMID: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.

摘要

背景

降胆固醇治疗已显示出多种有益效果；然而，其对氧化应激和内皮功能的影响尚未完全阐明。

目的

研究辛伐他汀和依折麦布对高脂血症患者多形核细胞线粒体功能及白细胞与内皮细胞相互作用的影响。

方法

39例高脂血症患者被随机分为两组：一组接受辛伐他汀（40毫克/天），另一组接受依折麦布（10毫克/天），为期4周，之后两组均接受联合治疗，为期4周。评估血脂谱、线粒体参数（氧消耗、活性氧（ROS）和膜电位）、谷胱甘肽水平、超氧化物歧化酶活性、过氧化氢酶活性以及白细胞/内皮细胞相互作用和黏附分子-VCAM-1、ICAM-1、E-选择素。

结果

单独使用辛伐他汀或依折麦布后血脂谱均有改善（低密度脂蛋白胆固醇：分别降低40.2%和19.6%），但前者效果更强（p<0.001），两者联合使用时进一步降低（低密度脂蛋白胆固醇：分别降低50.7%和56.8%）。除此之外，辛伐他汀、依折麦布以及辛伐他汀+依折麦布均显著增加氧消耗、膜电位和谷胱甘肽含量，并降低ROS水平，从而改善线粒体功能。此外，辛伐他汀+依折麦布增加过氧化氢酶活性。另外，辛伐他汀和辛伐他汀/依折麦布通过减少白细胞滚动和黏附以及增加白细胞滚动速度改善白细胞/内皮细胞相互作用。最后，辛伐他汀、依折麦布以及辛伐他汀+依折麦布降低黏附分子ICAM-1水平，依折麦布+辛伐他汀显著降低E-选择素水平。