Vaziri Nosratola D
Division of Nephrology and Hypertension, Departments of Medicine, Physiology and Biophysics, University of California, Irvine, California, USA.
Semin Dial. 2009 Nov-Dec;22(6):644-51. doi: 10.1111/j.1525-139X.2009.00661.x.
End-stage renal disease (ESRD) is associated with accelerated atherosclerosis and premature death from cardiovascular disease. These events are driven by oxidative stress inflammation and lipid disorders. ESRD-induced lipid abnormalities primarily stem from dysregulation of high-density lipoprotein (HDL), triglyceride-rich lipoprotein metabolism, and oxidative modification of lipoproteins. In this context, production and plasma concentration of Apo-I and Apo-II are reduced, HDL maturation is impaired, HDL composition is altered, HDL antioxidant and anti-inflammatory functions are depressed, clearance of triglyceride-rich lipoproteins and their atherogenic remnants is impaired, their composition is altered, and their plasma concentration is elevated in ESRD. The associated defect in HDL maturation is largely caused by acquired lecithin-cholesterol acyltransferase deficiency while its triglyceride enrichment is due to hepatic lipase deficiency. Hypertriglyceridemia, abnormal composition, and impaired clearance of triglyceride-rich lipoproteins and their remnants are mediated by down-regulation of lipoprotein lipase, hepatic lipase, very low-density lipoprotein (VLDL) receptor, and LDL receptor-related protein, relative reduction in ApoC-II/ApoC-III ratio, up-regulation of acyl-CoA cholesterol acyltransferase, and elevated plasma level of cholesterol ester-poor prebeta HDL. Impaired clearance and accumulation of oxidation-prone VLDL and chylomicron remnants and abnormal LDL composition in the face of oxidative stress and inflammation favors their uptake by macrophages and resident cells in the artery wall. The effect of heightened influx of lipids is compounded by impaired HDL-mediated reverse cholesterol transport leading to foam cell formation which is the central event in atherosclerosis plaque formation and subsequent plaque rupture, thrombosis, and tissue damage.
终末期肾病（ESRD）与动脉粥样硬化加速及心血管疾病导致的过早死亡相关。这些事件由氧化应激、炎症和脂质紊乱驱动。ESRD诱导的脂质异常主要源于高密度脂蛋白（HDL）失调、富含甘油三酯的脂蛋白代谢以及脂蛋白的氧化修饰。在这种情况下，载脂蛋白I（Apo-I）和载脂蛋白II（Apo-II）的产生及血浆浓度降低，HDL成熟受损，HDL组成改变，HDL抗氧化和抗炎功能受抑，富含甘油三酯的脂蛋白及其致动脉粥样硬化残余物的清除受损，其组成改变，且在ESRD中其血浆浓度升高。HDL成熟相关缺陷很大程度上由获得性卵磷脂胆固醇酰基转移酶缺乏引起，而其甘油三酯富集则归因于肝脂酶缺乏。高甘油三酯血症、富含甘油三酯的脂蛋白及其残余物的异常组成和清除受损是由脂蛋白脂肪酶、肝脂酶、极低密度脂蛋白（VLDL）受体和低密度脂蛋白受体相关蛋白的下调、ApoC-II/ApoC-III比值相对降低、酰基辅酶A胆固醇酰基转移酶上调以及胆固醇酯含量低的前β-HDL血浆水平升高介导的。面对氧化应激和炎症，易氧化的VLDL和乳糜微粒残余物的清除受损和积累以及LDL异常组成有利于它们被动脉壁中的巨噬细胞和驻留细胞摄取。脂质流入增加的影响因HDL介导的胆固醇逆向转运受损而加剧，导致泡沫细胞形成，这是动脉粥样硬化斑块形成以及随后斑块破裂、血栓形成和组织损伤的核心事件。
