The Interaction between Oxidised Chylomicron Remnants and the Aorta of Rats Fed a Normocholesterolaemic or Hypercholesterolaemic Diet

Abstract

The effects of oxidised chylomicron remnants on endothelium-dependent relaxation and lipoprotein uptake were studied in both the normocholesterolaemic and hypercholesterolaemic rat aorta in vitro. Incubation of aortic rings taken from normocholesterolaemic animals with oxidised (by treatment with copper sulphate) chylomicron remnant particles resulted in a reduction in both vessel sensitivity and maximum percent relaxation in response to carbachol (CCh) and ATP, without affecting responses to A23187 and S-nitroso-N-acetylpenicillamine (SNAP). Studies comparing control vessels and those taken from fat-fed rats confirmed that hypercholesterolaemia significantly decreased relaxations in response to CCh and potentiated contractions in response to phenylephrine (PE) via a nitric oxide (NO)-dependent mechanism. Perfusion of the aorta of these hypercholesterolaemic rats for 2 h with ¹²⁵I-labelled oxidised chylomicron remnants showed that significantly greater amounts of lipoprotein became associated with the artery wall, as compared to control normocholesterolaemic animals. However, there was no significant difference in the uptake of native chylomicron remnant particles between control and hypercholesterolaemic vessels. Taken together, the findings of this study suggest that incorporation of lipoproteins of dietary origin into the arterial wall may contribute to endothelial dysfunction and that their contribution may be enhanced by hypercholesterolaemia. These data also support the putative involvement of oxidative modification in the atherosclerotic process, although the presence of oxidised chylomicron remnants in vivo and their role in atherogenesis remains to be established.