Oxidation of chylomicron remnants and vascular dysfunction.

ABSTRACT

Recent evidence suggests that chylomicron remnants (CMRs), the lipoproteins which carry dietary lipids in the blood, may play a direct role in the initiation of atherosclerosis by influencing vascular function. Unlike low-density lipoprotein (LDL), CMR do not require prior oxidation to bring about potentially pro-atherogenic effects on vascular endothelial cell function and macrophage foam cell formation. However, CMR carry oxidized lipids from the diet and may also become oxidized in the body, thus it is important to establish how the oxidative state of the particles may modulate these effects. Pharmacological studies have demonstrated that oxidation of CMR significantly enhances their inhibitory effects on endothelium-dependent vascular relaxation and their potentiation of vasoconstriction in rat and pig arteries. In striking contrast to the effects of LDL oxidation, however, the induction of macrophage foam cell formation has been found to be inversely related to the oxidative state of CMR. Thus, oxidation of CMR has potentially pro-atherogenic effects on endothelial function, but appears to protect against foam cell generation. These findings indicate that the oxidative state of CMR may cause important changes in the atherogenicity of the particles.