Cytotoxicity of remnants of triglyceride-rich lipoproteins: an atherogenic insult?
None of more widely accepted theories of atherogenesis can explain all the more pertinent features of atherosclerosis: a) foam dell formation; b) endothelial cell stress/injury; c) protective effect of HDL; d) atherogenicity of triglyceride-rich lipoproteins; e) the vesicular nature of early lipid deposits in atherosclerosis, f) dissociation of diet risk from the risk due to elevation in plasma cholesterol; or g) correlation of postprandial lipemia with CAD risk. The data obtained from our studies provide a new theory of atherogenesis. This theory is that: a) lipolytic surface remnants of TG-rich lipoproteins may represent a major class of atherogenic lipoproteins which are exacerbated during postprandial hyperlipidemia; b) clearance of these surfaces remnants by HDL in vivo may be one important way that HDL prevents atherosclerosis; c) excess surface remnants may be linked to delayed clearance of potentially atherogenic core remnants, directly linked to atherogenicity via surface remnant-mediated cytotoxicity to cells of the artery wall and/or linked to the deposit of unesterified cholesterol-rich vesicles in early atherosclerosis. An appealing aspect of this hypothesis is that it can account for several unexplained features of atherosclerosis, such as anatomic differences in susceptibility to atherosclerosis in the vascular tree, the preference of early atherosclerosis in humans to the region of the coronary artery subjected to low hemodynamic shear stresses, and the vesicular nature of lipid deposits in early atherosclerosis.
Chung
B H
BH
Department of Medicine, University of Alabama, Birmingham.
Segrest
J P
JP
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood; D008066:Lipolysis / Q000502:physiology; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects; D014280:Triglycerides / Q000032:analysis*
D008074:Lipoproteins; D014280:Triglycerides