Natural antioxidants and atherosclerosis

The precursors of fibrous atherosclerotic plaques are fatty streaks, characterized by accumulation of fat laden macrophages beneath an intact endothelium. These macrophages are derived from monocytes in the circulating blood and the lipid is derived from plasma low density lipoprotein (LDL). But LDL is poorly taken up by monocytes/macrophages in vitro unless it has been oxidatively modified. Hence the phypothesis has developed that one determinant of atherosderosis is whether LDL becomes oxidized by free radicals in the subendothelial space. An epidemiological study of 12 European sub-populations which all have about the same plasma cholesterol concentration but quite different incidences of coronary heart disease (CHD) showed a significant inverse correlation of plasma a -tocopherol with CHD. In several animal models, vitamin E or some other antioxidants attenuate experimental atherosclerosis. Each particle of LDL contains about 8-12 molecules of tocopherol, 0.5 to 1 molecule of ubiquinol-10 and small amounts of carotenoids but other antioxidants in the extracellular fluid, notably (water-soluble) ascorbate protect against oxidative damage in in vitro experiments with human blood plasma. The ascorbate presumably acts by regeneration a -tocopherol from its one-electron oxidation product, the a-tocopheroxyl radical. The author found that the small amounts of ubiquinol present in LDL offer important protection against oxidation. Unlike vitamins C and E, ubiquinol is biosynthesized by humans but it is also obtained from the diet (some fatty fish are the richest sources). The ubiquinol content of plasma LDL was increased 4-fold by giving volunteers ubiquinone. Their plasma LDL was subsequently found more resistant against oxidation.