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Journal of Cardiovascular Translational Research

23-04-2024 | Dantrolene | Original Article

RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin

Authors: Yi Gao, Shuai Li, Xueyan Liu, Daoyuan Si, Weiwei Chen, Fenghua Yang, Huan Sun, Ping Yang

Published in: Journal of Cardiovascular Translational Research

Abstract

The effect of Ryanodine receptor2 (RyR2) and its stabilizer on cardiac hypertrophy is not well known. C57/BL6 mice underwent transverse aortic contraction (TAC) or sham surgery were administered dantrolene, the RyR2 stabilizer, or control drug. Dantrolene significantly alleviated TAC-induced cardiac hypertrophy in mice, and RNA sequencing was performed implying calcineurin/NFAT3 and TNF-α/NF-κB/NLRP3 as critical signaling pathways. Further expression analysis and Western blot with heart tissue as well as neonatal rat cardiomyocyte (NRCM) model confirmed dantrolene decreases the activation of calcineurin/NFAT3 signaling pathway and TNF-α/NF-κB/NLRP3 signaling pathway, which was similar to FK506 and might be attenuated by calcineurin overexpression. The present study shows for the first time that RyR2 stabilizer dantrolene attenuates cardiac hypertrophy by inhibiting the calcineurin, therefore downregulating the TNF-α/NF-κB/NLRP3 pathway.

Graphical Abstract

Schematic diagram of the mechanism of Dantrolene. Dantrolene attenuates cardiac hypertrophy through inhibition of TNF-α/NF-κB/NLRP3 pathway by downregulating Calcineurin/NFAT3 pathway.

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Title: RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin
Authors: Yi Gao
Shuai Li
Xueyan Liu
Daoyuan Si
Weiwei Chen
Fenghua Yang
Huan Sun
Ping Yang
Publication date: 23-04-2024
Publisher: Springer US
Keyword: Dantrolene
Published in: Journal of Cardiovascular Translational Research
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-023-10376-8

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RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-α/NF-κB/NLRP3 Signaling Pathway through Inhibiting Calcineurin

Abstract

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Abstract

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ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page