[Peripheral remnant metabolism]

Although in cross-sectional studies of men with premature CHD plasma triglycerides as well as LDL-cholesterol levels are almost invariably increased, the atherogenicity of plasma triglycerides has remained controversial, mainly because in most prospective studies triglycerides have failed to survive the test of multivariate analysis as an independent risk factor. On the other hand the atherosclerotic risk is increased in some genetic disorders associated with elevated triglyceride levels and also in patients with remnant hyperlipidemia coexistence of non-functional apo E isoforms with a genetic or acquired disorder of VLDL/IDL metabolism lead to the accumulation of remnant lipoproteins (beta-VLDL) with a prolonged half life which are finally metabolized in macrophages leading to foam cell formation. Similar remnant particles have been described as hypertriglyceridemic-VLDL1 (HTG-VLDL1) in patients with hypertriglyceridemia. At least two metabolic pathways are involved in the cellular uptake of remnant lipoproteins. One is identical with the classical LDL-Apo B, E receptor, which binds these particles by either the apo B or apo E moiety. The other binding site may be related to the LRP-type (LDL-receptor-like protein) remnant receptor which recognizes functional apo E isoforms. In addition beta-VLDL and oxidatively modified remnant lipoproteins are recognized by the scavenger receptor of macrophages leading to cholesterylester accumulation. The oxidized remnant lipoproteins may be also cytotoxic for endothelial cells as it has been shown extensively for the atherogenic oxidized LDL. Among the peripheral cells macrophages, endothelial cells and also vascular smooth muscle cells are the major cell types which are affected by atherogenic remnant lipoprotein particles.(ABSTRACT TRUNCATED AT 250 WORDS)