Morena M, Cristol J P, Dantoine T, Carbonneau M A, Descomps B, Canaud B
Department of Biochemistry, Lapeyronie Hospital, University of Montpellier, France.
Nephrol Dial Transplant. 2000 Mar;15(3):389-95. doi: 10.1093/ndt/15.3.389.
Cardiovascular diseases represent the major cause of mortality in haemodialysis (HD) patients. Oxidized low-density lipoprotein (Ox-LDL) is a major cardiovascular risk factor, implicated in atherosclerotic plaque formation. It has been suggested that high-density lipoprotein (HD) has the capacity to reduce the oxidative modifications of LDL. The aim of this study is to analyse the protective effects of HDL in HD patients.
In vitro copper-induced LDL oxidation was evaluated in 12 patients with chronic renal failure (mean age 61.0+/-12.8 years) and compared to 25 healthy subjects (mean age 57.3+/-19.2 years). LDL were incubated in oxygen-saturated PBS, LDL oxidation was initiated by Cu (II) in the presence and absence of HDL and assessed by measuring the absorbance (abs) increase at 234 nm due to conjugated diene formation. Duration of lag time, maximum velocity (V(max.)) of lipid peroxidation, oxidation slope and half-time of maximum diene formation (T (1/2)) were obtained by kinetic modelling analysis.
HDL (1.06+/-0.31 vs 1.23+/-0.39 mmol/l) and Apo AI (1. 17+/-0.39 vs 1.49+/-0.20 g/l) levels were decreased in HD patients. In the absence of HDL, LDL obtained from HD patients showed an enhanced susceptibility to oxidation in vitro as demonstrated by the significant decrease in lag time (54.5+/-22.2 vs 79.4+/-37.8 min) and a significant increase in V(max.) (0.026+/-0.006 vs 0.017+/-0. 005 abs/min). In all cases, HDL (from 0.1 to 2 microM) prevented LDL oxidation in vitro; however, this effect was significantly reduced in HD patients: increase in lag time 54.2% vs 150.4% in HD vs controls; increase in T (1/2) 52.2% vs 124.6% in HD vs controls; decrease in V(max). 13.5% vs 38.5% in HD vs controls.
These results suggest that qualitative abnormalities such as an impairment of HDL-associated enzymes are associated with a decrease of HDL levels during HD. Hence, in addition to the known impairment of reverse cholesterol transport, the reduction of HDL protective capacity against oxidative stress could be involved in the development of HD-induced atherosclerosis.
心血管疾病是血液透析（HD）患者死亡的主要原因。氧化型低密度脂蛋白（Ox-LDL）是主要的心血管危险因素，与动脉粥样硬化斑块形成有关。有人提出高密度脂蛋白（HDL）具有减少低密度脂蛋白（LDL）氧化修饰的能力。本研究的目的是分析HDL对HD患者的保护作用。
评估了12例慢性肾衰竭患者（平均年龄61.0±12.8岁）体外铜诱导的LDL氧化情况，并与25名健康受试者（平均年龄57.3±19.2岁）进行比较。将LDL在饱和氧的磷酸盐缓冲盐水中孵育，在有和没有HDL的情况下用铜（II）引发LDL氧化，并通过测量234nm处由于共轭二烯形成导致的吸光度（abs）增加来评估。通过动力学建模分析获得延迟时间、脂质过氧化的最大速度（V(max.)）、氧化斜率和最大二烯形成的半衰期（T(1/2)）。
HD患者的HDL（1.06±0.31 vs 1.23±0.39 mmol/l）和载脂蛋白AI（Apo AI）（1.17±0.39 vs 1.49±0.20 g/l）水平降低。在没有HDL的情况下，HD患者的LDL在体外表现出对氧化的易感性增强，这表现为延迟时间显著缩短（54.5±22.2 vs 79.4±37.8分钟）和V(max.)显著增加（0.026±0.006 vs 0.017±0.005 abs/分钟）。在所有情况下，HDL（0.1至2 microM）均可在体外防止LDL氧化；然而，HD患者的这种作用显著降低：HD患者与对照组相比，延迟时间增加54.2% vs 150.4%；T(1/2)增加52.2% vs 124.6%；V(max.)降低13.5% vs 38.5%。
这些结果表明，诸如HDL相关酶受损等质量异常与HD期间HDL水平降低有关。因此，除了已知的逆向胆固醇转运受损外，HDL对氧化应激保护能力的降低可能参与了HD诱导的动脉粥样硬化的发展。
