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CD36 Plays a Role in Murine Thrombosis Induced by Vascular Injury
Author(s) -
Li Wei,
Ghosh Arunima,
Chen kan,
Febbraio Maria,
Silverstein Roy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.902.3
Subject(s) - cd36 , platelet , platelet activation , chemistry , thrombosis , reactive oxygen species , in vivo , plasminogen activator , medicine , receptor , biology , biochemistry , microbiology and biotechnology
We previously showed that the Type B scavenger receptor, CD36 mediates platelet responses to oxidized phospholipids. Using a FeCl 3 ‐induced injury model and CD36 knockout (KO) and wild type (WT) mice, we examined the role of CD36 in thrombosis by in vivo video‐microscopy after injection of Rhodamine 6G to label platelets. While there was no difference in time to thrombosis (TTT) in carotid arteries using 12.5% FeCl 3 , when a less severe injury was induced by 7.5% FeCl 3 , there was increased TTT in KOs (p=0.006). We also observed increased TTT in both arterioles and venules of KOs (p<0.05). Mechanistically, we previously showed that platelet signaling via CD36 was mediated by MAP kinases. Here we demonstrate a significantly elongated TTT in the carotid artery in irradiated thrombocytopenic WT mice transfused with JNK inhibitor pre‐treated WT platelets. No effect was observed using KO platelets. Isolated platelets from KOs were less sensitive to activation in vitro by low dose ADP. Immunohistochemical analysis of carotid thrombi showed a significant decrease in the endothelial cell marker CD105 in KOs, suggesting less accumulation of endothelial cell‐derived microparticles. Plasma urokinase type plasminogen activator levels were increased in KO mice after induction of thrombi. By direct injection of the superoxide indicator hydroethidine, we also found that the level of FeCl 3 injury induced reactive oxygen species was lower in KOs. We conclude that CD36 plays a complex role in thrombosis via MAP kinase mediated modulation of platelets activation, promotion of reactive oxygen species formation after endothelial injury, and regulation of activation of the fibrinolytic system.