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.

Toll-like receptor 4 activation in platelets from myocardial infarction patients / Barilla, F.; Cammisotto, V.; Bartimoccia, S.; Loffredo, L.; Nocella, C.; Bruno, N.; Torromeo, C.; Rosa, P.; Viceconte, N.; Pignatelli, P.; Gaudio, C.; Carnevale, R.; Violi, F.. - In: THROMBOSIS RESEARCH. - ISSN 0049-3848. - 209:(2022), pp. 33-40. [10.1016/j.thromres.2021.11.019]

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

Cammisotto V.
Co-primo
;
Bartimoccia S.;Loffredo L.;Nocella C.;Bruno N.;Torromeo C.;Rosa P.;Viceconte N.;Pignatelli P.;Gaudio C.;Carnevale R.
Penultimo
;
Violi F.
Ultimo
2022

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.
2022
lipopolysaccharides; myocardial infarction; platelets; thrombosis; toll-like receptor 4; blood platelets; humans; lipopolysaccharides; membrane glycoproteins; receptors, interleukin-1; myocardial infarction; toll-like receptor 4
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Toll-like receptor 4 activation in platelets from myocardial infarction patients / Barilla, F.; Cammisotto, V.; Bartimoccia, S.; Loffredo, L.; Nocella, C.; Bruno, N.; Torromeo, C.; Rosa, P.; Viceconte, N.; Pignatelli, P.; Gaudio, C.; Carnevale, R.; Violi, F.. - In: THROMBOSIS RESEARCH. - ISSN 0049-3848. - 209:(2022), pp. 33-40. [10.1016/j.thromres.2021.11.019]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1629311
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