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Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis

Cardiac dysfunction is manifested as decline of cardiac systolic function, and multiple cardiovascular diseases (CVDs) can develop cardiac insufficiency. Mitochondrial antiviral signaling (MAVS) is known as an innate immune regulator involved in viral infectious diseases and autoimmune diseases, whe...

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Autores principales: Wang, Qian, Sun, Zhenzhen, Cao, Shihan, Lin, Xiuli, Wu, Mengying, Li, Yuanyuan, Yin, Jie, Zhou, Wei, Huang, Songming, Zhang, Aihua, Zhang, Yue, Xia, Weiwei, Jia, Zhanjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283757/
https://www.ncbi.nlm.nih.gov/pubmed/35844503
http://dx.doi.org/10.3389/fimmu.2022.919038
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author Wang, Qian
Sun, Zhenzhen
Cao, Shihan
Lin, Xiuli
Wu, Mengying
Li, Yuanyuan
Yin, Jie
Zhou, Wei
Huang, Songming
Zhang, Aihua
Zhang, Yue
Xia, Weiwei
Jia, Zhanjun
author_facet Wang, Qian
Sun, Zhenzhen
Cao, Shihan
Lin, Xiuli
Wu, Mengying
Li, Yuanyuan
Yin, Jie
Zhou, Wei
Huang, Songming
Zhang, Aihua
Zhang, Yue
Xia, Weiwei
Jia, Zhanjun
author_sort Wang, Qian
collection PubMed
description Cardiac dysfunction is manifested as decline of cardiac systolic function, and multiple cardiovascular diseases (CVDs) can develop cardiac insufficiency. Mitochondrial antiviral signaling (MAVS) is known as an innate immune regulator involved in viral infectious diseases and autoimmune diseases, whereas its role in the heart remains obscure. The alteration of MAVS was analyzed in animal models with non-hypertrophic and hypertrophic cardiac dysfunction. Then, MAVS-deficient mice were generated to examine the heart function, mitochondrial status and energy metabolism. In vitro, CRISPR/Cas9-based gene editing was used to delete MAVS in H9C2 cell lines and the phenotypes of mitochondria and energy metabolism were evaluated. Here we observed reduced MAVS expression in cardiac tissue from several non-hypertrophic cardiac dysfunction models, contrasting to the enhanced MAVS in hypertrophic heart. Furthermore, we examined the heart function in mice with partial or total MAVS deficiency and found spontaneously developed cardiac pump dysfunction and cardiac dilation as assessed by echocardiography parameters. Metabonomic results suggested MAVS deletion probably promoted cardiac dysfunction by disturbing energy metabolism, especially lipid metabolism. Disordered and mitochondrial homeostasis induced by mitochondrial oxidative stress and mitophagy impairment also advanced the progression of cardiac dysfunction of mice without MAVS. Knockout of MAVS using CRISPR/Cas9 in cardiomyocytes damaged mitochondrial structure and function, as well as increased mitochondrial ROS production. Therefore, reduced MAVS contributed to the pathogenesis of non-hypertrophic cardiac dysfunction, which reveals a link between a key regulator of immunity (MAVS) and heart function.
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spelling pubmed-92837572022-07-16 Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis Wang, Qian Sun, Zhenzhen Cao, Shihan Lin, Xiuli Wu, Mengying Li, Yuanyuan Yin, Jie Zhou, Wei Huang, Songming Zhang, Aihua Zhang, Yue Xia, Weiwei Jia, Zhanjun Front Immunol Immunology Cardiac dysfunction is manifested as decline of cardiac systolic function, and multiple cardiovascular diseases (CVDs) can develop cardiac insufficiency. Mitochondrial antiviral signaling (MAVS) is known as an innate immune regulator involved in viral infectious diseases and autoimmune diseases, whereas its role in the heart remains obscure. The alteration of MAVS was analyzed in animal models with non-hypertrophic and hypertrophic cardiac dysfunction. Then, MAVS-deficient mice were generated to examine the heart function, mitochondrial status and energy metabolism. In vitro, CRISPR/Cas9-based gene editing was used to delete MAVS in H9C2 cell lines and the phenotypes of mitochondria and energy metabolism were evaluated. Here we observed reduced MAVS expression in cardiac tissue from several non-hypertrophic cardiac dysfunction models, contrasting to the enhanced MAVS in hypertrophic heart. Furthermore, we examined the heart function in mice with partial or total MAVS deficiency and found spontaneously developed cardiac pump dysfunction and cardiac dilation as assessed by echocardiography parameters. Metabonomic results suggested MAVS deletion probably promoted cardiac dysfunction by disturbing energy metabolism, especially lipid metabolism. Disordered and mitochondrial homeostasis induced by mitochondrial oxidative stress and mitophagy impairment also advanced the progression of cardiac dysfunction of mice without MAVS. Knockout of MAVS using CRISPR/Cas9 in cardiomyocytes damaged mitochondrial structure and function, as well as increased mitochondrial ROS production. Therefore, reduced MAVS contributed to the pathogenesis of non-hypertrophic cardiac dysfunction, which reveals a link between a key regulator of immunity (MAVS) and heart function. Frontiers Media S.A. 2022-07-01 /pmc/articles/PMC9283757/ /pubmed/35844503 http://dx.doi.org/10.3389/fimmu.2022.919038 Text en Copyright © 2022 Wang, Sun, Cao, Lin, Wu, Li, Yin, Zhou, Huang, Zhang, Zhang, Xia and Jia https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Qian
Sun, Zhenzhen
Cao, Shihan
Lin, Xiuli
Wu, Mengying
Li, Yuanyuan
Yin, Jie
Zhou, Wei
Huang, Songming
Zhang, Aihua
Zhang, Yue
Xia, Weiwei
Jia, Zhanjun
Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis
title Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis
title_full Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis
title_fullStr Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis
title_full_unstemmed Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis
title_short Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis
title_sort reduced immunity regulator mavs contributes to non-hypertrophic cardiac dysfunction by disturbing energy metabolism and mitochondrial homeostasis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283757/
https://www.ncbi.nlm.nih.gov/pubmed/35844503
http://dx.doi.org/10.3389/fimmu.2022.919038
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