Retention of chylomicron remnants by arterial tissue; importance of an efficient clearance mechanism from plasma

Atherosclerosis is thought to begin with the trapping of cholesterol rich l ipoproteins within the intima of arterial vessels. Thereafter a complex inf lammatory cascade involving recruitment and transformation of leukocytes, a ccumulation of sterols in macrophages and cellular proliferation, can lead to a progressive occlusion in blood flow, or an unstable arterial lesion pr one to prothrombotic events. Primary intervention strategies aimed at reduc ing atherogenesis are designed to achieve reductions in sterol rich lipopro teins, primarily low density lipoproteins, given the hypothesis that decrea sed exposure will attenuate the rate of arterial cholesterol accumulation. Epidemiological evidence has clearly identified a positive relationship bet ween poor dietary (fat) habits and the onset and progression of atheroscler osis. However lipoproteins which mediate the transport of dietary lipid, th at is chylomicrons, are not normally considered to be directly involved in atherogenesis, because of their larger size and inability to efficiently pe netrate arterial tissue. In contrast, this article reviews recent evidence which suggests that once chylomicrons are hydrolysed to their remnant form, the triglyceride depleted chylomicron remnants penetrate arterial tissue a nd moreover, become preferentially trapped within the subendothelial space as concentrated focii. Ongoing studies demonstrate that significant chylomi cron remnant accumulation can occur in a number of primary and secondary li pid disorders and in normolipidemic subjects with coronary artery disease. Chylomicron remnant dyslipidemia in conditions prone to premature atheroscl erosis is consistent with the putative atherogenicity of these particles an d can be explained by increased arterial exposure to cholesterol rich chylo micron remnants. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved .