Trimethylamine N-oxide promotes tissue factor expression and activity in vascular endothelial cells: A new link between trimethylamine N-oxide and atherosclerotic thrombosis.
Thromb Res
; 177: 110-116, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30875490
ABSTRACT
Trimethylamine-N-oxide (TMAO), one of the products in choline metabolite, is recently reported to be associated with cardiovascular diseases (CVD) that mainly attribute to atherothrombosis. However, the mechanisms how TMAO functions in the pathogenesis of CVD and atherothrombosis remain elusive. Tissue factor (TF) has been implicated in the thrombogenicity of atherosclerotic plaques. In the present study, we demonstrated that TMAO promoted TF (but not TF pathway inhibitor) expression via activation of NF-κB signaling pathway in primary human coronary artery endothelial cells (HCAECs). TMAO strongly increased TF activity and thrombin production. Further, a small dose of TMAO significantly increased TF expression and nuclear translocation of NF-κB with the synergistic action of low-dose of pro-atherosclerotic factors, such as TNF-α and HMGB1. Importantly, plasma TMAO level was positively correlated with TF activity in patients with ST-elevation myocardial infarction (STEMI). Altogether, our data revealed that TMAO promoted thrombosis through increasing TF expression and activity. The understanding of the new link between TMAO and atherothrombosis may facilitate therapeutic strategy in the prevention and treatment of atherothrombosis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose
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Tromboplastina
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Células Endoteliais
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Aterosclerose
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Metilaminas
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article