title: Enhanced macrophage uptake of lipoprotein(a) after Ca2+-induced aggregate-formation.
abstract: We tested the hypothesis that aggregated lipoprotein(a) [Lp(a)] is avidly taken up by macrophages. Lp(a) was isolated by sequential centrifugations and gel chromatography from a patient with high plasma levels of Lp(a) who was being treated with low density lipoprotein (LDL)-apheresis. Aggregated Lp(a) was prepared by mixing native Lp(a) with 2.5 mmol/L CaCl2, and 54% of the 125I-Lp(a) aggregated after interacting with CaCl2. The binding and degradation of aggregated Lp(a) in macrophages were 4.6- and 4.7-fold higher than those of native Lp(a), respectively. An excess amount of LDL did not inhibit either increase. Cholesterol esterification in macrophages was markedly stimulated by aggregated Lp(a), and macrophages were transformed into foam cells. Cytochalasin 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) accumulation, thereby contributing to the acceleration of atherosclerosis.
authors.affiliation: Second Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu.
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Yashiro
authors.forename: H
authors.initials: H
authors.lastname: Tasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
mesh_terms: D000368:Aged; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000096:biosynthesis; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004951:Esterification / Q000187:drug effects; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics*; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects
chemical_list: D002788:Cholesterol Esters; D017270:Lipoprotein(a); D003571:Cytochalasin B; D002784:Cholesterol; D002118:Calcium