LDL-platelet interaction under oxidative stress induces macrophage foam cell formation.
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.
Aviram
M
M
Lipid Research Laboratory, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion, Israel.
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010743:Phospholipids / Q000378:metabolism; D015539:Platelet Activation; D012701:Serotonin / Q000494:pharmacology
D008077:Lipoproteins, LDL; D008563:Membrane Lipids; D010743:Phospholipids; D012701:Serotonin; D002784:Cholesterol; D007501:Iron