Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis.
In the last decade, it was recognized that platelets and lipoproteins play a pivotal role in both early and late atherogenesis. Beside cellular interactions of platelets with other blood cells and vascular cells, interactions with lipoproteins seem to be quite important. Lipoproteins are fundamental 'players' in atherogenesis since they change the properties of different cells involved in atherosclerosis and thrombosis. Several studies have already shown that low density lipoproteins (LDL) are involved in the initiation of platelet signalling pathways. Platelets of hypercholesterolemic patients show hyperaggregability in vitro and enhanced activity in vivo. This review elucidates the major aspects concerning how native and modified lipoproteins influence the activation and metabolic behaviour of platelets, and shows a new way by which platelet-mediated lipoprotein transfer might contribute to foam cell formation. In hyperlipidaemia, circulating platelets are activated. This is accompanied by increased platelet aggregation, platelet-leukocyte aggregate formation, and platelet-induced superoxide anion production. Furthermore, oxidized LDL induces monocyte adhesion to the endothelium, migration and proliferation of smooth muscle cells, injures cells, interferes with nitric oxide release, and promotes procoagulant properties of vascular cells. New data about platelet-mediated lipoprotein transport and consequent foam cell formation, however, provide proof of how platelets might contribute to atheromatous lesion formation.
Siegel-Axel
Dorothea
D
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Otfried-Müller Str. 10, D-72076 Tübingen, Germany. dorothea.axel@med.uni-tuebingen.de
Daub
Karin
K
Seizer
Peter
P
Lindemann
Stephan
S
Gawaz
Meinrad
M
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010587:Phagocytosis; D015539:Platelet Activation; D051116:Receptors, Scavenger / Q000378:metabolism; D015398:Signal Transduction
D008074:Lipoproteins; D008077:Lipoproteins, LDL; D051116:Receptors, Scavenger; C099252:oxidized low density lipoprotein