title: Platelet-modified low density lipoprotein induces macrophage cholesterol accumulation and platelet activation.
abstract: Low density lipoprotein (LDL), modified by chemical or biological means, was shown to induce macrophage cholesterol accumulation. The cholesterol and protein contents of LDL were decreased (by 10 and 15%, respectively) by incubation of the LDL for 2 h at 37 degrees C with normal washed platelet suspension or with platelet-conditioned medium; these decreases were not affected by platelet activation. The platelet-modified LDL caused a greater increase (by up to 15%) in collagen-induced, in vitro platelet aggregation than control LDL. Incubation of mouse peritoneal macrophages with platelet-modified LDL for 18 h at 37 degrees C resulted in an elevation of the macrophage cholesterol ester content (by 35-50%) as well as an increase in the cholesterol esterification rate (by 40-70%), compared with the effect of control LDL. Macrophage cholesterol synthesis, however, was significantly decreased (by 40-50%), compared with the effect of control LDL. The effect of LDL treated by platelet-conditioned medium was similar to that of platelet-modified LDL. The effect of platelet-modified LDL on macrophage cholesterol esterification was maximal within 24 h of incubation, and it was not significantly affected by inhibition of cholesterol synthesis. The platelet-modified LDL was taken up by the macrophages in a saturable fashion and its uptake was competitively inhibited by LDL, but not by acetylated LDL. We conclude that platelet-modified LDL interacts with the LDL receptor and induces macrophage cholesterol accumulation. Since the modified lipoprotein induces in vitro foam cell formation and platelet activation, platelet-modified LDL could be considered to be pro-atherogenic.
authors.affiliation: Lipid Research Unit, Rambam Medical Center, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Aviram
authors.forename: B
authors.initials: B
authors.lastname: Fuhrman
authors.forename: S
authors.initials: S
authors.lastname: Keidar
authors.forename: I
authors.initials: I
authors.lastname: Maor
authors.forename: M
authors.initials: M
authors.lastname: Rosenblat
authors.forename: G
authors.initials: G
authors.lastname: Dankner
authors.forename: G
authors.initials: G
authors.lastname: Brook
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000032:analysis / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology; D008264:Macrophages / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D008077:Lipoproteins, LDL; D016718:Arachidonic Acid; D003094:Collagen; D002784:Cholesterol; D008148:Lovastatin; D013917:Thrombin