Cholesterol oxides in plasma and lipoproteins of magnesium-deficient rabbits and effects of their lipoproteins on endothelial barrier function.
The cholesterol oxide (ChO) levels in the plasma and low density lipoproteins (LDL and VLDL) in four groups of rabbits fed for seven weeks either normal (NC) or high cholesterol (HC) with low or normal magnesium (Mg) diets were determined and compared with the NC group fed a standard rabbit diet. The plasma from the NC group contained low levels of different cholesterol oxides. These cholesterol oxides were significantly elevated in the plasma of rabbits fed a HC-normal magnesium or a HC-low magnesium diet. In the NC-low Mg group, 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol and 7-ketocholesterol were elevated while the other cholesterol oxides remained within the normal range of the NC group. When the cholesterol oxides were assayed in the LDL and VLDL fractions as micrograms/mg protein, the fractions obtained from the groups fed NC-low Mg, HC-normal Mg or HC-low Mg diets showed higher levels of cholesterol oxides than the fractions obtained from the NC group. When LDL and VLDL fractions from the different groups were incubated at equal protein concentration with confluent endothelial cell monolayers, transendothelial albumin transfer was significantly increased by the lipoproteins from the experimental groups as compared to the control group. These results suggest that elevation of cholesterol oxides in magnesium deficiency or hypercholesterolaemia may be related to their atherogenic effects through decreasing the endothelial barrier function which could enhance the deposition of cholesterol rich lipoproteins into the arterial wall.