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- W4241663089 abstract "Background: Platelets are important regulators of vascular thrombosis and inflammation, and are known to express toll-like receptors (TLRs). The functional significance of these platelet-TLR pathways in acute myocardial infarction (AMI) has not been fully examined but may contribute to persistent thrombo-inflammatory responses after AMI. This study examined platelet-TLR expression and TLR-mediated platelet activation in healthy and AMI subjects, and also examined TLR-mediated platelet inflammatory responses in healthy subjects. Methods and Results: When examined by western blotting, platelets from AMI patients exhibited significant upregulation of TLR1 and TLR4 and slight, but non-significant, upregulation of TLR2. When examined by flow cytometry, platelets from healthy and AMI subjects became similarly activated in response to TLR2, TLR1 and TLR4 stimulation. This was despite treatment with antiplatelet therapy in the AMI cohort. To demonstrate the effect of antiplatelet therapy on TLR-mediated platelet activation, a randomised trial was conducted on healthy subjects and activation was measured by flow cytometry. It showed that 1-week treatment with dual antiplatelet therapy (aspirin and ticagrelor) only moderately inhibited TLR2-mediated, TLR1-mediated, and TLR4-mediated platelet activation. In vitro co-culture experiments demonstrated that platelets regulate leukocyte pro-inflammatory responses to TLR stimulation in a TLR agonist-specific manner. Specifically, platelets attenuated leukocyte activation (measured by flow cytometry) and cytokine and chemokine production (by multiplex enzyme-linked immunosorbent assay (ELISA)) in response to TLR stimulation. Conclusion: These platelet-TLR pathways differentially regulated a number of thrombotic and inflammatory responses in both healthy and AMI subjects. Importantly, platelet-TLRs remained functional in AMI patients, despite treatment with antiplatelet therapy." @default.
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- W4241663089 date "2019-01-01" @default.
- W4241663089 modified "2023-09-26" @default.
- W4241663089 title "Platelet Toll-Like Receptor Expression and Toll-Like Receptor-Mediated Platelet Responses in Healthy and Acute Myocardial Infarction Subjects" @default.
- W4241663089 doi "https://doi.org/10.1016/j.hlc.2019.05.007" @default.
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