Enhanced LDL oxidation in uremic patients: An additional mechanism for accelerated atherosclerosis?

Abstract

Since oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL, LDL oxidation was investigated in uremic patients who often develop accelerated atherogenesis. Three groups of uremic patients were studied (10 on predialysis conservative therapy, 11 on repetitive hemodialysis, 13 on peritoneal dialysis) and compared with seventy matched controls. LDL oxidation was evaluated in all patients as: (i) the susceptibility to in vitro oxidation (by measuring the resistance to Cu(++)-induced formation of conjugated dienes), (ii) vitamin E concentration in LDL, and (iii) presence of plasma anti-oxidized LDL antibodies, expressed as the ratio anti-oxLDL/anti-nativeLDL antibodies. The lipid profile was studied in all patients. Vitamin E concentration did not differ between the various groups, although LDL from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier generation of conjugated dienes and by the presence of an higher antibody ratio) compared to control subjects. Subclass analysis of the different patients revealed that peritoneal dialysis treatment ameliorated the oxidation markers. However, a prolonged dialytic treatment caused a decrease in vitamin E concentration in LDL and increased their susceptibility to oxidation.

Paraoxonase activity and antibodies to oxidized-LDL in chronic renal failure patients on renal replacement therapy

“…Oxidation of LDL is recognized as a key stage in the early development of atherosclerosis (6). Increased LDL susceptibility to oxidation has been reported in CRF, a condition characterized by accelerated atherogenesis and derangement of lipoprotein metabolism (7).…”

Impact of Dyslipidemia in End-Stage Renal Disease

“…The LDL-C has also been shown to be qualitatively different from normal LDL-C in that there is an increased concentration of small, dense particles together with the high apo B (38). In addition, increased oxidized LDL levels (31)(32)(33) and increased Lp(a) levels have been reported in peritoneal dialysis patients, with 42% of patients having levels above the 75th percentile (34). The hypertriglyceridemia in peritoneal dialysis patients may be partially explained by increased hepatic synthesis of VLDL, which binds triglycerides (38).…”

α‐Tocopherol mediated peroxidation in the copper (II) and met myoglobininduced oxidation of human low density lipoprotein: The influence of lipid hydroperoxides

“…These results are consistent with the finding that the resistance of LDL oxidation to copper is idiosyncratic with respect to the donor, even when LDL is prepared under identical conditions, and this can be partially ascribed to variation in the content of endogenous lipid hydroperoxides and ~-tocopherol [11,13,14]. Indeed, the decreased resistance of LDL to copper dependent oxidation found in groups of subjects at greater risk from developing atherosclerosis supports the further extension of this idea to include the possibility that readily oxidised LDL may be pro-atherogenic [34][35][36].…”