OXIDATION OF HEPARIN-ISOLATED LDL BY HEMIN - THE EFFECT OF SERUM COMPONENTS

Oxidation of low-density lipoprotein (LDL) in the artery wall is proba bly determined by several factors, some of which may include physiolog ical oxidants such as heme and hydrogen peroxide, blood serum componen ts, and the interaction of the lipoprotein with glycosaminoglycans. Gl ycosaminoglycans form complexes with LDL that increase its susceptibil ity to oxidation in vitro. To examine the effect of these factors on o xidation of LDL in vitro, we isolated LDL from serum by using heparin and oxidized the resolubilized lipoprotein (Hep-LDL) with hemin and hy drogen peroxide in the presence of apolipoprotein B lipoprotein-defici ent serum (BLPDS). Low levels (2.1%) of BLPDS stimulated the oxidation of Hep-LDL by approximately fivefold, and increasing concentrations r educed oxidation to baseline rates. By comparison, the oxidation of na tive LDL was stimulated to a similar extent at lower concentrations of BLPDS (0.83%) and returned to baseline more rapidly with increasing l evels of the serum fraction. Oxidation rates did not change significan tly with increasing concentrations of BLPDS alone. Human serum albumin (HSA) at comparable levels produced changes in the oxidation of Hep-L DL similar to those seen with BLPDS. Degradation of heme was accelerat ed 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 mu mol/L) . This antioxidant also effectively inhibited oxidation of Hep-LDL max imally stimulated by BLPDS. The data suggest that serum components, pa rticularly HSA, modulate the peroxidation of both glycosaminoglycan-tr eated LDL and native LDL by hemin and hydrogen peroxide via mechanisms that may involve oxidative interactions between heme and HSA. This ph enomenon may influence oxidation of LDL in vivo, where levels of HSA i n regions of the artery wall are comparable with levels that stimulate the oxidation of Hep-LDL in vitro.