Toll-like receptor 4 activation in platelets from myocardial infarction patients.
Thromb Res
; 209: 33-40, 2022 Jan.
Article
in En
| MEDLINE
| ID: mdl-34856494
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toll-Like Receptor 4
/
Myocardial Infarction
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Thromb Res
Year:
2022
Document type:
Article