Protective effects of high-density lipoprotein against oxidative stress are impaired in haemodialysis patients

Introduction. Cardiovascular diseases represent the major cause of mortalit y in haemodialysis (HD) patients. Oxidized low-density lipoprotein (Ox-LDL) is a major cardiovascular risk factor, implicated in atherosclerotic plaqu e formation. It has been suggested that high-density lipoprotein (HD) has t he capacity to reduce; the oxidative modifications of LDL. The aim of this study is to analyse the protective effects of HDL in HD patients. Methods. 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 oxyge n-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 vel ocity (V-max.) of lipid peroxidation, oxidation slope and half-time of maxi mum diene formation (T1/2) were obtained by kinetic modelling analysis. Results. HDL (1.06+/-0.31 vs 1.23+/-0.39 mmol/l) and Apo GI (1.17+/-0.39 vs 1.49+/-0.20 g/l) levels were decreased in HD patients. In the absence of H DL, LDL obtained from HD patients showed an enhanced susceptibility to oxid ation 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 mu M) pre vented LDL oxidation in vitro; however, this effect was significantly reduc ed in HD patients: increase in lag time 54.2% vs 150.4% in HD vs controls; increase in T1/2 52.2% vs 124.6% in HD vs controls; decrease in V-max. 13.5 % vs 38.5% in HD vs controls. Conclusions. These results suggest that qualitative abnormalities such as a n impairment of HDL-associated enzymes are associated with a decrease of HD L levels during I-ID. Hence, in addition to the known impairment of reverse cholesterol transport, the reduction of HDL protective capacity against ox idative stress could be involved in the development of HD-induced atheroscl erosis.