Lipoprotein Heterogeneity and Apolipoprotein B Metabolism

Abstract

The apolipoprotein B containing lipoproteins VLDL, IDL, and LDL exhibit variation in their structure, function, and metabolism. These major lipoprotein classes can be fractionated into apparently discrete components by density gradient centrifugation or affinity chromatography. Examination of the behavior of subfractions in vivo reveals the presence of metabolic channels within the VLDL-LDL delipidation cascade so that the pedigree of a lipoprotein in part determines its metabolic fate. Evidence from VLDL and LDL apoB turnovers together with epidemiological data allows the construction of a quantitative model for the generation of small, dense LDL. This lipoprotein subspecies is one component of the dyslipidemic syndrome known as the atherogenic lipoprotein phenotype, a common disorder in those at risk for coronary heart disease. Understanding lipoprotein heterogeneity is an essential step in the further discovery of the pathogenesis of atherosclerosis and in the tailoring of pharmacologic treatment for subjects at risk.