Characterization and determinants of an electronegatively charged low-density lipoprotein in human plasma

Abstract

There is evidence that oxidative modification of low density lipoprotein (LDL) is an important step in the atherosclerotic process. Electronegatively charged LDL has been found in the atherosclerotic lesions of rabbit and human and it is supposed to represent an early modification of LDL in the oxidative process in vivo. We describe a chromatographic method for determination of an LDL subfraction (LDL⁻) percentage from plasma LDL and the investigation of the lipid composition of native LDL and LDL⁻ fractions separated by this method. We also studied the main determinants of the change in plasma LDL⁻ level in a population sample of 45 men during a 6-months follow-up period. The LDL⁻ fraction separated by anion-exchange chromatography had significantly higher triglyceride and free cholesterol and significantly lower phospholipid and total cholesterol contents, and lower a-tocopherol to triglyceride ratio than native LDL. In a 6-month follow up of 45 subjects, decreases in the ratio of blood glutathione disulphide to reduced glutathione, in serum LDL cholesterol and in serum n-3 polyunsaturated fatty acids, and an increase in plasma p-carotene concentration had independent associations with a decrease of LDL ⁻. The linear regression model including only these four variables was able to account for 47% of the variation of LDL ⁻. Our findings suggest that the change in the plasma LDL⁻ percentage measured by an anion-exchange liquid chromatography is predicted by changes in the major determinants of lipid peroxidation.