NLRP3 deficiency accelerates pressure overload-induced cardiac remodeling via increased TLR4 expression

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Fang-Fang LiWen-Hao Qian

Abstract

NLRP3, a member of the nucleotide-binding oligomerization domain (NOD)-like receptor family, is involved in cardiac inflammation. However, the functional role of NLRP3 in cardiac remodeling is not clear. To investigate the roles of NLRP3 in pressure overload-induced cardiac remodeling, NLRP3 knockout and wild-type mice were subjected to aortic banding to induce cardiac remodeling. The data showed that NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated cardiac hypertrophy, fibrosis, and inflammation responses with deteriorating cardiac dysfunction in the pressure overload-induced cardiac remodeling mouse model. Neonatal rat cardiomyocytes were isolated and stimulated with phenylephrine (PE). We identified NLRP3 as a negative regulator of cardiomyocyte remodeling in PE-stimulated cardiomyocyte remodeling using adenovirus-NLRP3 and NLRP3 siRNA. Mechanistically, we found that the expression of Toll-like receptor (TLR) 4 was upregulated in NLRP3-deficient mouse hearts and PE-stimulated cardiomyocytes. NLRP3 knockout mice subjected to a TLR4 inhibitor revealed a relieved cardiac remodeling response with improved cardiac dysfunction. Our data suggested that NLRP3 could be a therapeutic target fo...Continue Reading

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Citations

Feb 15, 2020·Scandinavian Journal of Clinical and Laboratory Investigation·Antun FerenčićHrvoje Jakovac
Jun 9, 2020·Clinical and Translational Medicine·Yucheng WangRuizhen Chen
Jul 29, 2021·Arquivos brasileiros de cardiologia·Pedro Henrique Rizzi AlvesCamila Renata Corrêa
Jul 16, 2021·Journal of Cardiovascular Pharmacology and Therapeutics·Sergey V PopovJames M Downey
Jul 8, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Fangfang LiQing Li
Oct 7, 2021·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Maria L DiasFiona B McDonald

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Datasets Mentioned

BETA
GTX27481

Methods Mentioned

BETA
light microscopy
electrophoresis
transfection

Software Mentioned

Pro Plus
Image

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