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.