Diminished susceptibility to in vitro oxidation of low-density lipoproteins in hypercholesterolemia: key role of alpha-tocopherol content

Abstract

Oxidizability of low-density lipoproteins (LDL) in hypercholesterolemia is of clinical relevance, but previous studies revealed diverging results. Therefore, we studied ex vivo oxidation of LDL in plasma samples of 57 hypercholesterolemic and 20 normocholesterolemic volunteers. LDL were isolated by ultracentrifugation and analyzed for lipids and α-tocopherol. The formation of conjugated dienes, lipoperoxides and malondialdehyde was measured at 0.1 μmol/l LDL, 3.2 μmol/l CuSO 4. We found prolongation of the lagtime (53.6/65.8/71.4 min) with tertiles (≤3.17/3.89/14.2 mmol/l) of LDL-cholesterol (LDL-C). Regression analysis revealed that the lagtime increased with the apparent concentrations of cholesterol ( P=0.003) and α-tocopherol ( P=0.001) in the oxidation assay. A multiple regression model with the apparent concentrations of α-tocopherol, triglycerides and cholesterol explained 40% of the variation in lagtime. The close relationship between plasma concentrations of LDL-C and LDL-α-tocopherol ( P=0.002) indicated that LDL contained more of this antioxidant in hypercholesterolemia. This might provide an explanation for the positive relationship between lagtime and LDL-C. The latter was independent of whether LDL-C or LDL-protein was chosen for standardization of the oxidation assay. The formation of conjugated dienes ( P=0.000), lipoperoxides ( P=0.038) and malondialdehyde ( P=0.001) increased with the cholesterol level in the assay. This may be due to the increased load of LDL with cholesterol esters as a substrate for oxidation in hypercholesterolemia. Our data do not support the opinion that hypercholesterolemia is characterized by increased susceptibility of LDL to oxidation.