ENHANCED MACROPHAGE UPTAKE OF LIPOPROTEIN(A) AFTER CA2-INDUCED AGGREGATE-FORMATION()

We tested the hypothesis that aggregated lipoprotein(a) [Lp(a)] is avi dly taken up by macrophages. Lp(a) was isolated by sequential centrifu gations and gel chromatography from a patient with high plasma levels oi Lp(a) who was being treated with low density lipoprotein (LDL)-aphe resis. Aggregated Lp(a) was prepared by mixing native Lp(a) with 2.5 m mol/L CaCl2, and 54% of the I-125-Lp(a) aggregated after interacting w ith CaCl2. The binding and degradation of aggregated Lp(a) in macropha ges were 4.4- and 4.7-fold higher than those of native Lp(a), respecti vely. An excess amount of LDL did not inhibit either increase. Cholest erol esterification in macrophages was markedly stimulated by aggregat ed Lp(a), and macrophages were transformed into foam cells. Cytochalas in B, a phagocytosis inhibitor, strongly inhibited the degradation and cholesterol esterification (78 and 83%, respectively). These findings suggested that aggregation may be partially involved in Lp(a) accumul ation, thereby contributing to the acceleration of atherosclerosis.