Radical-mediated oxidation of isolated human very-low-density lipoprotein.

Abstract

Oxidative modification of human low-density lipoprotein (LDL) has received much attention because of its suggested involvement in the early events of atherogenesis. In contrast, little data exist concerning the oxidation of human very-low-density lipoprotein (VLDL), although such modification promotes foam cell formation by these lipoproteins. We therefore investigated the radical-mediated oxidation of VLDL by using controlled oxidizing conditions and sensitive and specific methods to assess lipoprotein lipid oxidation and antioxidation. We observed that the ratio of alpha-tocopherol to coenzyme Q10 in VLDL was close to that of LDL, suggesting that these lipoproteins may transport some coenzyme Q10 to extrahepatic tissues, as they do tocopherol. Most of the coenzyme Q10 associated with VLDL was present in its reduced, antioxidant active form, ubiquinol-10. The small amounts of ubiquinol-10 in VLDL provided the lipoprotein lipids with a highly efficient antioxidant protection. Also, the kinetics of radical-mediated lipid peroxidation in VLDL resembled that in LDL and therefore also probably proceeded via the recently described tocopherol-mediated peroxidation mechanism. Oxidation competition experiments using aqueous radicals and physiological concentrations and molar ratios of LDL and VLDL indicated that in contrast to the situation with high-density lipoproteins, lipid peroxidation was initiated and detected simultaneously in the former two lipoprotein particles. However, once initiated, peroxidation propagated at an approximately twofold higher rate in VLDL than LDL. Our studies suggest that radical-mediated lipid (per)oxidation proceeds via similar mechanisms in isolated LDL and VLDL. We conclude that efficient LDL antioxidants are also likely to be effective protective agents for VLDL.