NLRP3 inflammasome contributes to endothelial dysfunction in angiotensin II-induced hypertension in mice.
Microvasc Res
; 143: 104384, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35618036
ABSTRACT
AIMS:
Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension. MATERIALS ANDMETHODS:
We analyzed blood pressure and vascular function of wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice, treated with Ang II. In vitro, we mainly tested the endothelial nitric oxide synthase (eNOS) phosphorylation expression of human umbilical vein endothelial cells (HUVECs). KEYFINDINGS:
Here we showed that 14-day Ang II infusion into mice resulted in the elevation of blood pressure, NLRP3 expression, serum interleukin (IL)-1ß level, and the decline of endothelium-dependent relaxation function, p-eNOS-Ser1177 expression in aortas. Nlrp3 deficiency reduced Ang II-induced blood pressure elevation and endothelial dysfunction. In vitro, NLRP3 was involved in the effect of Ang II on reducing p-eNOS-Ser1177 expression. Moreover, the direct effect of IL-1ß on vascular endothelial injury could be observed in both vivo and vitro.SIGNIFICANCE:
Our result demonstrates that the NLRP3 inflammasome is critically involved in the detrimental effects of Ang II on vascular endothelium in hypertension via the activation of IL-1ß, placing NLRP3 as a potential target for therapeutic interventions in conditions with endothelial dysfunction in hypertension.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inflamassomos
/
Hipertensão
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Microvasc Res
Ano de publicação:
2022
Tipo de documento:
Article