NONOXIDATIVE MODIFICATION OF NATIVE LOW-DENSITY-LIPOPROTEIN BY OXIDIZED LOW-DENSITY-LIPOPROTEIN

The oxidative modification of low-density lipoprotein (LDL) has been i mplicated in the pathogenesis of atherosclerosis, although little is k nown as yet about the precise mechanism of oxidation in vivo. The stud ies presented here demonstrate that, in the absence of cells or transi tion metals, oxidized LDL can modify native LDL through co-incubation ill vitro such as to increase its net negative charge, in a concentrat ion-dependent manner. The interaction is not inhibited by peroxyl radi cal scavengers or metal chelators, precluding the possibility that the modification of native LDL by oxidized LDL is through an oxidative pr ocess, Studies with radioiodinated oxidized LDL showed no transfer of radioactivity to the native LDL, demonstrating that fragmentation of p rotein and the transfer of some of the fragments does not account for the modified charge on the native LDL particle. The adjacency of nativ e to oxidized LDL in the arterial wall may be a potential mechanism by which the altered recognition properties of the apolipoprotein B-100 may arise rapidly without oxidation or extensive modification of the n ative LDL lipid itself.