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- W4247130894 abstract "Introduction: Platelet hyperreactivity, common in many pathophysiological conditions, is associated with increased atherothrombotic risk. Platelet hyperreactivity, specifically in dyslipidemia, has been mechanistically linked to accumulation in circulation of specific oxidized phospholipids (oxPC CD36 ), ligands for pattern-recognition receptor CD36. Although significant progress in understanding of CD36 mediated signaling in platelets has been made in recent years, many details of the molecular mechanism are still missing. Hypothesis: CD36 is known to cooperate with other receptors in cells such as macrophages during inflammation and apoptosis. Moreover, we have recently reported that platelets can also respond to oxidation specific epitopes via Toll Like Receptors. So, we hypothesized that TLRs may have a role in oxPC CD36 induced platelet activation. Methods and Results: In this study, using in vitro approaches as well as mice with genetic deletion of MyD88 or TLRs, we demonstrate that TLR2 is required for platelet activation by oxPC CD36 . oxPC CD36 induce formation of CD36/TLR2/TLR6 complex in platelets and downstream signaling via TIRAP-MyD88-IRAK1/4-TRAF6, which leads to platelet integrin activation via the SFK-Syk-PLCγ2 pathway. Studies in hyperlipidemic ApoE -/- mice have demonstrated that TLR2 deficiency abolishes platelet hyperreactivity and accelerated thrombosis induced by hyperlipidemia. At the same time, no effect of TLR2 deficiency on platelet activation nor thrombosis was observed in normolipidemic mice. Conclusions: Taken together, our studies reveal that TLR2 plays a key role in platelet hyperreactivity and the prothrombotic state in the settings of hyperlipidemia by sensing a wide range of endogenous lipid-peroxidation ligands and activating innate immune signaling cascade in platelets." @default.
- W4247130894 created "2022-05-12" @default.
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- W4247130894 date "2017-05-01" @default.
- W4247130894 modified "2023-10-16" @default.
- W4247130894 title "Abstract 50: TLR2 Plays A Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia" @default.
- W4247130894 doi "https://doi.org/10.1161/atvb.37.suppl_1.50" @default.
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