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.