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

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.

• Authors: Francesco Barillà, Vittoria Cammisotto, Simona Bartimoccia, Lorenzo Loffredo, Cristina Nocella, Noemi Bruno, Concetta Torromeo, Paolo Rosa, Nicola Viceconte, Pasquale Pignatelli, Carlo Gaudio, Roberto Carnevale, Francesco Violi
• Journal: Thrombosis research (Thromb Res) Vol. 209 Pg. 33-40 (Jan 2022) ISSN: 1879-2472 [Electronic] United States
• PMID: 34856494 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Lipopolysaccharides
• Membrane Glycoproteins
• Receptors, Interleukin-1
• Toll-Like Receptor 4

Topics

• Blood Platelets
• Humans
• Lipopolysaccharides (pharmacology)
• Membrane Glycoproteins
• Myocardial Infarction
• Receptors, Interleukin-1
• Toll-Like Receptor 4