TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion.
Eur Heart J
; 36(22): 1394-404, 2015 Jun 07.
Article
en En
| MEDLINE
| ID: mdl-25755115
ABSTRACT
AIMS:
Superficial erosion of atheromata causes many acute coronary syndromes, but arises from unknown mechanisms. This study tested the hypothesis that Toll-like receptor-2 (TLR2) activation contributes to endothelial apoptosis and denudation and thus contributes to the pathogenesis of superficial erosion. METHODS ANDRESULTS:
Toll-like receptor-2 and neutrophils localized at sites of superficially eroded human plaques. In vitro, TLR2 ligands (including hyaluronan, a matrix macromolecule abundant in eroded lesions) induced endothelial stress, characterized by reactive oxygen species production, endoplasmic reticulum (ER) stress, and apoptosis. Co-incubation of neutrophils with endothelial cells (ECs) potentiated these effects and induced EC apoptosis and detachment. We then categorized human atherosclerotic plaques (n = 56) based on morphologic features associated with superficial erosion, 'stable' fibrotic, or 'vulnerable' lesions. Morphometric analyses of the human atheromata localized neutrophils and neutrophil extracellular traps (NETs) near clusters of apoptotic ECs in smooth muscle cell (SMC)-rich plaques. The number of luminal apoptotic ECs correlated with neutrophil accumulation, amount of NETs, and TLR2 staining in SMC-rich plaques, but not in 'vulnerable' atheromata.CONCLUSION:
These in vitro observations and analyses of human plaques indicate that TLR2 stimulation followed by neutrophil participation may render smooth muscle cell-rich plaques susceptible to superficial erosion and thrombotic complications by inducing ER stress, apoptosis, and favouring detachment of EC.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Apoptosis
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Receptor Toll-Like 2
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Placa Aterosclerótica
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Neutrófilos
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article