title: Retention of chylomicron remnants by arterial tissue; importance of an efficient clearance mechanism from plasma.
abstract: Atherosclerosis is thought to begin with the trapping of cholesterol rich lipoproteins within the intima of arterial vessels. Thereafter a complex inflammatory cascade involving recruitment and transformation of leukocytes, accumulation of sterols in macrophages and cellular proliferation, can lead to a progressive occlusion in blood flow, or an unstable arterial lesion prone to prothrombotic events. Primary intervention strategies aimed at reducing atherogenesis are designed to achieve reductions in sterol rich lipoproteins, primarily low density lipoproteins, given the hypothesis that decreased exposure will attenuate the rate of arterial cholesterol accumulation. Epidemiological evidence has clearly identified a positive relationship between poor dietary (fat) habits and the onset and progression of atherosclerosis. However lipoproteins which mediate the transport of dietary lipid, that is chylomicrons, are not normally considered to be directly involved in atherogenesis, because of their larger size and inability to efficiently penetrate 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 and moreover, become preferentially trapped within the subendothelial space as concentrated focii. Ongoing studies demonstrate that significant chylomicron remnant accumulation can occur in a number of primary and secondary lipid disorders and in normolipidemic subjects with coronary artery disease. Chylomicron remnant dyslipidemia in conditions prone to premature atherosclerosis is consistent with the putative atherogenicity of these particles and can be explained by increased arterial exposure to cholesterol rich chylomicron remnants.
authors.affiliation: Department of Medicine, University of Western Australia, Perth, Australia. jmamo@cyllene.uwa.edu.au
authors.forename: J C
authors.initials: JC
authors.lastname: Mamo
authors.forename: S D
authors.initials: SD
authors.lastname: Proctor
authors.forename: D
authors.initials: D
authors.lastname: Smith
mesh_terms: D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology*; D002914:Chylomicrons / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans
chemical_list: D002914:Chylomicrons; D004041:Dietary Fats