Vitamin C protects low-density lipoprotein from homocysteine-mediated oxidation

Homocysteine, an atherogenic amino acid, promotes iron-dependent oxidation of low-density lipoprotein (LDL). We investigated whether vitamin C, a physiological antioxidant, could protect LDL from homocysteine-mediated oxidation. LDL (0.2 mg of protein/ml) was incubated at 37°C with homocysteine (1000 μM) and ferric iron (10–100 μM) in either the absence (control) or presence of vitamin C (5–250 μM). Under these conditions, vitamin C protected LDL from oxidation as evidenced by an increased lag time preceding lipid diene formation (≥ 5 vs. 2.5 h for control), decreased thiobarbituric acid-reactive substances accumulation (≤ 19 ± 1 nmol/mg when vitamin C ≥ 10 μM vs. 32 ± 3 nmol/mg for control, p < .01), and decreased lipoprotein anodic electrophoretic mobility. Near-maximal protection was observed at vitamin C concentrations similar to those in human blood (50–100 μM); also, some protection was observed even at low concentrations (5–10 μM). This effect resulted neither from altered iron redox chemistry nor enhanced recycling of vitamin E in LDL. Instead, similar to previous reports for copper-dependent LDL oxidation, we found that vitamin C protected LDL from homocysteine-mediated oxidation through covalent lipoprotein modification involving dehydroascorbic acid. Protection of LDL from homocysteine-mediated oxidation by vitamin C may have implications for the prevention of cardiovascular disease.