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 com- bination 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

Barillà, F. (2021). Toll-like receptor 4 activation in platelets from myocardial infarction patients. THROMBOSIS RESEARCH [10.1016/j.thromres.2021.11.019].

Toll-like receptor 4 activation in platelets from myocardial infarction patients

Barillà, Francesco
2021-11-24

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 com- bination 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
24-nov-2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE
English
Lipopolysaccharides Myocardial infarction Platelets Toll-like receptor 4 Thrombosis
https://doi.org/10.1016/j.thromres.2021.11.019
Barillà, F. (2021). Toll-like receptor 4 activation in platelets from myocardial infarction patients. THROMBOSIS RESEARCH [10.1016/j.thromres.2021.11.019].
Barillà, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/312622
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