高胆固醇血症患者的脂蛋白分离术介导人内皮细胞中的血管保护基因表达。
Lipoprotein apheresis of hypercholesterolemic patients mediates vasoprotective gene expression in human endothelial cells.
作者信息
Morawietz Henning, Goettsch Winfried, Brux Melanie, Reimann Manja, Bornstein Stefan R, Julius Ulrich, Ziemssen Tjalf
机构信息
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Clinical Center, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstr 74, 01307 Dresden, Germany.
出版信息
Atheroscler Suppl. 2013 Jan;14(1):107-13. doi: 10.1016/j.atherosclerosissup.2012.10.013.
OBJECTIVE
Hypercholesterolemia is an important risk factor of cardiovascular diseases. Lipoprotein apheresis is an efficient strategy to reduce the serum low-density lipoprotein (LDL)-cholesterol and lipoprotein(a) levels and cardiovascular complications in patients with severe hypercholesterolemia. The underlying molecular mechanisms are not well-understood. In this study, we analyzed the impact of lipoprotein apheresis on gene expression in human endothelial cells.
METHODS
Human endothelial cells were stimulated with serum of hypercholesterolemic patients before and after lipoprotein apheresis. The expression of endothelial lipoprotein receptors, nitric oxide (NO) synthase and adhesion molecules was quantified by real-time PCR and Western blot.
RESULTS
Lipoprotein apheresis reduced the expression of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells. Low-density lipoprotein (LDL) receptor expression remained unchanged. The mRNA expression of the endothelial nitric oxide synthase (eNOS) was increased with serum of hypercholesterolemic patients after lipoprotein apheresis. In contrast, endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) was reduced in response to serum after lipoprotein apheresis.
CONCLUSION
Lipoprotein apheresis reduced the expression of the proatherosclerotic oxLDL receptor LOX-1 and adhesion molecule VCAM-1 and increased the expression of vasoprotective and NO generating eNOS in human endothelial cells in response to serum of hypercholesterolemic patients. These novel molecular mechanisms may account for the antiatherosclerotic and vasoprotective potential of lipoprotein apheresis in patients with hypercholesterolemia.
目的
高胆固醇血症是心血管疾病的重要危险因素。脂蛋白分离术是降低严重高胆固醇血症患者血清低密度脂蛋白（LDL）胆固醇和脂蛋白（a）水平以及心血管并发症的有效策略。其潜在的分子机制尚不清楚。在本研究中，我们分析了脂蛋白分离术对人内皮细胞基因表达的影响。
方法
用人内皮细胞分别与脂蛋白分离术前、后高胆固醇血症患者的血清进行孵育。通过实时聚合酶链反应（PCR）和蛋白质免疫印迹法（Western blot）对内皮脂蛋白受体、一氧化氮（NO）合酶和黏附分子的表达进行定量分析。
结果
脂蛋白分离术降低了内皮细胞中凝集素样氧化型低密度脂蛋白受体1（LOX-1）的表达。低密度脂蛋白（LDL）受体表达未发生变化。脂蛋白分离术后，高胆固醇血症患者血清可使内皮型一氧化氮合酶（eNOS）的mRNA表达增加。相反，脂蛋白分离术后，血管细胞黏附分子1（VCAM-1）的内皮表达随血清作用而降低。
结论
脂蛋白分离术可降低动脉粥样硬化前氧化型低密度脂蛋白受体LOX-1和黏附分子VCAM-1的表达，并增加人内皮细胞中具有血管保护作用且能产生NO的eNOS的表达，这可能是脂蛋白分离术对高胆固醇血症患者具有抗动脉粥样硬化和血管保护作用的新分子机制。
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