LDL-platelet interaction under oxidative stress induces macrophage foam cell formation

Abstract

The atherosclerotic lesion consists of macrophages filled with cholesterol derived from oxidized-low density lipoprotein (Ox-LDL) and also contains platelet aggregates. Under oxidative stress on platelet activation, and enhanced macrophage uptake of Ox-LDL (secondary to platelet-mediated modification of the lipoprotein or to the interaction between Ox-LDL and arterial wall macrophages). The following data demonstrate that all of these mechanisms are operable in vitro: 1) upon platelet incubation with Ox-LDL, platelet aggregation and release are substantially increased; 2) under oxidative stress (in the presence of ferrous ions) platelets' phospholipids are oxidized, paralleled by increased platelets activation; 3) platelet conditioned medium (PCM) from collagen activated platelets, can modify LDL to a form which is taken up by macrophages at enhanced rate; 4) under oxidative stress (in the presence of copper ions) platelets can oxidatively modify native LDL; 5) PCM increases macrophage uptake of Ox-LDL, secondary to the stimulatory effect of PDGF (which is present in PCM) on the macrophage receptors for Ox-LDL. In conclusion, we suggest that the involvement of platelets in macrophage foam cell formation is related to platelet released factors which can either oxidize the LDL or increase the uptake of Ox-LDL by the macrophages. These effects of platelets on Ox-LDL, as well as the activation of blood platelets by Ox-LDL, contribute to the formation of the atherosclerotic lesion.