NFAT5 mediates hypertonic stress-induced atherosclerosis via activating NLRP3 inflammasome in endothelium.
Cell Commun Signal
; 17(1): 102, 2019 08 20.
Article
em En
| MEDLINE
| ID: mdl-31429763
ABSTRACT
BACKGROUND:
How high-salt intake leads to the occurrence of many cardiovascular diseases such as atherosclerosis is a fundamental question in pathology. Here we postulated that high-salt-induced NFAT5 controls the inflammasome activation by directly regulating NLRP3, which mediates the expression of inflammatory- and adhesion-related genes in vascular endothelium, resulting in the formation of atherosclerosis.METHODS:
Atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice which accumulate cholesterol ester-enriched particles in the blood due to poor lipoprotein clearance capacity were used as the atherosclerosis model in vivo. Cultured endothelial cells (ECs) and monocytes under high-salt condition were used to explore the atheroprone role of the activation of NFAT5-NLRP3 inflammasome in vascular endothelium in vitro. Bioinformatic analysis and chromatin immunoprecipitation assay were used to identify the DNA binding sites of NFAT5 on promoters of NLRP3 and IL-1ß.RESULTS:
We first observe that high-salt intake promotes atherosclerosis formation in the aortas of ApoE-/- mice, through inducing the expression of NFAT5, NLRP3, and IL-1ß in endothelium. Overexpression of NFAT5 activates NLRP3-inflammasome and increases the secretion of IL-1ß in ECs partly via ROS. Chromatin immunoprecipitation assay demonstrates that NFAT5 directly binds to the promoter regions of NLRP3 and IL-1ß in endothelial cells subjected to the high-salt environment.CONCLUSIONS:
Our study identifies NFAT5 as a new and essential transcription factor that is required for the early activation of NLRP3-inflammasome-mediated endothelium innate immunity, contributing to the formation of atherosclerosis under hypertonic stress induction.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Endotélio Vascular
/
Aterosclerose
/
Inflamassomos
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Commun Signal
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China