Oxidation of heparin-isolated LDL by hemin. The effect of serum components.

Abstract

Oxidation of low-density lipoprotein (LDL) in the artery wall is probably determined by several factors, some of which may include physiological oxidants such as heme and hydrogen peroxide, blood serum components, and the interaction of the lipoprotein with glycosaminoglycans. Glycosaminoglycans form complexes with LDL that increase its susceptibility to oxidation in vitro. To examine the effect of these factors on oxidation of LDL from serum by using heparin and oxidized the resolubilized lipoprotein (Hep-LDL) with hemin and hydrogen peroxide in the presence of apolipoprotein B lipoprotein-deficient serum (BLPDS). Low levels (2.1%) of BLPDS stimulated the oxidation of Hep-LDL by approximately fivefold, and increasing concentrations reduced oxidation to baseline rates. By comparison, the oxidation of native LDL was stimulated to a similar extent at lower concentrations of BLPDS (0.83%) and returned to baseline more rapidly with increasing levels of the serum fraction. Oxidation rates did not change significantly with increasing concentrations of BLPDS alone. Human serum albumin (HSA) at comparable levels produced changes in the oxidation of Hep-LDL similar to those seen with BLPDS. Degradation of heme was accelerated by low levels of BLPDS or HSA in the presence of hydrogen peroxide but not by higher levels, and maximal degradation rates were inhibited by comparatively low levels of butylated hydroxytoluene (35 mumol/L). This antioxidant also effectively inhibited oxidation of Hep-LDL maximally stimulated by BLPDS. The data suggest that serum components, particularly HSA, modulate the peroxidation of both glycosaminoglycan-treated LDL and native LDL by hemin and hydrogen peroxide via mechanisms that may involve oxidative interactions between heme and HSA. This phenomenon may influence oxidation of LDL in vivo, where levels of HSA in regions of the artery wall are comparable with levels that stimulate the oxidation of Hep-LDL in vitro.