β2AR against myocarditis-lipid deposition depends on estrogenic environment in stress

in Journal of Endocrinology
Authors:
Xi Tao Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu, China

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https://orcid.org/0000-0002-7606-0363
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Yaxin Xu Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu, China

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Joseph Adu-Amankwaah Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu, China

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Zheng Gong The School of Public Affairs & Governance, Silliman University, Dumaguete, Negros, Philippines

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Yuxuan Wang The Second Clinical School of Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China

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Fei Huang Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu, China

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Hong Sun Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu, China

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https://orcid.org/0000-0003-2135-3107

Correspondence should be addressed to H Sun: sunh@xzhmu.edu.cn
DOI:
https://doi.org/10.1530/JOE-22-0335
Volume/Issue:
Volume 256: Issue 3
Article Type:
Research Article
Article ID:
e220335
Online Publication Date:
16 Feb 2023
Copyright:
© Society for Endocrinology 2023
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Cardiac lipid accumulation and inflammation have been linked to stress. There is mounting evidence that estrogen reduces lipid deposition and has anti-inflammatory properties; however, the exact mechanism is unknown. Recent studies showed that NLRP3 inflammasome is a key trigger of cardiac inflammation, and it is also involved in the progression of metabolic diseases. This study investigated the crucial role of the NLRP3 inflammasome in lipid accumulation during stress and the regulatory mechanism of estrogen in this process. Stress models were established by isoproterenol treatments in mice and H9c2 cells. With 5 mM isoproterenol, NLRP3 inflammasome activation was observed earlier at 0.5 h than that of lipid accumulation at 1 h in H9c2 cells. At 1 h after stress, the isoproterenol concentration required for NLRP3 inflammasome activation was lower compared to the concentration required for lipid deposition in mice myocardia and H9c2 cells; the former required 210 mg/kg or 10 μM for activation while the latter required 280 mg/kg or 5 mM. Knocking out or inhibiting NLRP3 inflammasome reduced myocardial lipid accumulation caused by stress in the mice myocardia and H9c2 cells. Estrogen downregulated NLRP3 inflammasome and reduced lipid accumulation in cardiomyocytes during stress. Finally, the anti-inflammatory and lipid-lowering effect of estrogen disappeared in β2ARKO mice and H9c2 cells pre-treated with ICI118,551. In conclusion, the upregulation of NLRP3 inflammasome induced by stress led to myocardial lipid accumulation, and β2AR downregulated NLRP3 inflammasome thereby reducing lipid accumulation which was dependent on the estrogenic environment.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2023
Article ID:
e220335
Article Type:
Research Article
Received Date:
29 Dec 2022
Accepted Date:
11 Jan 2023
Print Publication Date:
01 Mar 2023
Online Publication Date:
16 Feb 2023
Keywords:
NLRP3 inflammasome; lipid deposition; estrogen; β2AR

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