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Article Abstract
Introduction: Platelet toll-like receptor 4 (TLR4) is overexpressed in patients with myocardial infarction (MI) but it remains to elucidate if it is activated and the potential trigger.
Methods: Serum levels of lipopolysaccharides (LPS) and platelet aggregation (PA) by collagen alone or in combination with a TLR4 inhibitor (TLR4i) were studied ex vivo in platelets from 40 MI patients and 40 controls matched for age, sex and atherosclerotic risk factors; platelet TIR domain-containing adaptor protein (TIRAP) and TIRAP-MyD88 interaction were also investigated by western blot and co-immunoprecipitation, respectively. In vitro experiments were conducted to see if LPS triggers platelet TIRAP phosphorylation.
Results: Serum LPS was significantly higher in patients compared to controls (29.5±7.1 vs 16.2±3.8 pg/mL; p<0.001). Collagen-stimulated platelets from MI pre-treated with TLR4i showed a significant decrease of PA compared to platelets stimulated with collagen. Ex vivo study showed that TIRAP phosphorylation as well as TIRAP-MyD88 co-immunoprecipitation were higher in patients compared to controls. In vitro study showed that LPS, at concentrations like those found in MI, dose-dependently activated TIRAP and amplified the platelet response to the agonist, an effect blunted by TLR4i.
Conclusion: The study provides evidence that in MI patients platelet TLR4 is activated and suggests circulating LPS as potential trigger.
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| http://dx.doi.org/10.1016/j.thromres.2021.11.019 | DOI Listing |
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