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Human Lpa can be fractionated into two species with different affinities for lysine-Sepharose. Forty to 81% of the total Lpa in the density fraction 1.055-1.15 g/ml from five individuals was retained by this affinity column. The remaining unretained Lpa species with no apparently functional lysine binding site was similar to the retained species in its electrophoretic mobility, lipid, protein, and apolipoprotein composition, and the heterogeneity was not related to apoa size polymorphism. Interaction of the two species with the low density lipoprotein (LDL) receptor was studied in human fibroblasts. Using gold-labeled lipoproteins and an immunochemical procedure, both Lpa species could be located in clusters on the cell surface, but the extent of labeling was far lower than that seen with LDL. Both Lpa variants were less effective than LDL in 1) down-regulation of LDL-receptor activity; 2) suppression of cellular sterol synthesis; and 3) stimulation of cholesteryl ester formation in human fibroblasts. Although degradation of both species of Lpa by the perfused rat liver was stimulated after estrogen induction of hepatic LDL-receptor activity, the stimulation amounted to only a quarter of that seen with LDL. The heterogeneity of Lpa with respect to the ability to bind epsilon-aminocarboxylic acid will need to be considered in studying the physiological role of this lipoprotein. Both Lpa species exhibited a similar interaction with the LDL-receptor in vitro, and confirmed previous investigations that Lpa is only a poor ligand for the LDL-receptor.
Armstrong et al. (Thu,) studied this question.