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IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression

IL-12α plays an important role in modulating inflammatory response, fibroblast proliferation and angiogenesis through modulating macrophage polarization or T cell function, but its effect on cardiorespiratory fitness is not clear. Here, we studied the effect of IL-12α on cardiac inflammation, hypert...

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Autores principales: Bhattarai, Umesh, He, Xiaochen, Xu, Rui, Liu, Xiaoguang, Pan, Lihong, Sun, Yuxiang, Chen, Jian-Xiong, Chen, Yingjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969090/
https://www.ncbi.nlm.nih.gov/pubmed/36860846
http://dx.doi.org/10.3389/fimmu.2023.1105664
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author Bhattarai, Umesh
He, Xiaochen
Xu, Rui
Liu, Xiaoguang
Pan, Lihong
Sun, Yuxiang
Chen, Jian-Xiong
Chen, Yingjie
author_facet Bhattarai, Umesh
He, Xiaochen
Xu, Rui
Liu, Xiaoguang
Pan, Lihong
Sun, Yuxiang
Chen, Jian-Xiong
Chen, Yingjie
author_sort Bhattarai, Umesh
collection PubMed
description IL-12α plays an important role in modulating inflammatory response, fibroblast proliferation and angiogenesis through modulating macrophage polarization or T cell function, but its effect on cardiorespiratory fitness is not clear. Here, we studied the effect of IL-12α on cardiac inflammation, hypertrophy, dysfunction, and lung remodeling in IL-12α gene knockout (KO) mice in response to chronic systolic pressure overload produced by transverse aortic constriction (TAC). Our results showed that IL-12α KO significantly ameliorated TAC-induced left ventricular (LV) failure, as evidenced by a smaller decrease of LV ejection fraction. IL-12α KO also exhibited significantly attenuated TAC-induced increase of LV weight, left atrial weight, lung weight, right ventricular weight, and the ratios of them in comparison to body weight or tibial length. In addition, IL-12α KO showed significantly attenuated TAC-induced LV leukocyte infiltration, fibrosis, cardiomyocyte hypertrophy, and lung inflammation and remodeling (such as lung fibrosis and vessel muscularization). Moreover, IL-12α KO displayed significantly attenuated TAC-induced activation of CD4(+) T cells and CD8(+) T cells in the lung. Furthermore, IL-12α KO showed significantly suppressed accumulation and activation of pulmonary macrophages and dendritic cells. Taken together, these findings indicate that inhibition of IL-12α is effective in attenuating systolic overload-induced cardiac inflammation, heart failure development, promoting transition from LV failure to lung remodeling and right ventricular hypertrophy.
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spelling pubmed-99690902023-02-28 IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression Bhattarai, Umesh He, Xiaochen Xu, Rui Liu, Xiaoguang Pan, Lihong Sun, Yuxiang Chen, Jian-Xiong Chen, Yingjie Front Immunol Immunology IL-12α plays an important role in modulating inflammatory response, fibroblast proliferation and angiogenesis through modulating macrophage polarization or T cell function, but its effect on cardiorespiratory fitness is not clear. Here, we studied the effect of IL-12α on cardiac inflammation, hypertrophy, dysfunction, and lung remodeling in IL-12α gene knockout (KO) mice in response to chronic systolic pressure overload produced by transverse aortic constriction (TAC). Our results showed that IL-12α KO significantly ameliorated TAC-induced left ventricular (LV) failure, as evidenced by a smaller decrease of LV ejection fraction. IL-12α KO also exhibited significantly attenuated TAC-induced increase of LV weight, left atrial weight, lung weight, right ventricular weight, and the ratios of them in comparison to body weight or tibial length. In addition, IL-12α KO showed significantly attenuated TAC-induced LV leukocyte infiltration, fibrosis, cardiomyocyte hypertrophy, and lung inflammation and remodeling (such as lung fibrosis and vessel muscularization). Moreover, IL-12α KO displayed significantly attenuated TAC-induced activation of CD4(+) T cells and CD8(+) T cells in the lung. Furthermore, IL-12α KO showed significantly suppressed accumulation and activation of pulmonary macrophages and dendritic cells. Taken together, these findings indicate that inhibition of IL-12α is effective in attenuating systolic overload-induced cardiac inflammation, heart failure development, promoting transition from LV failure to lung remodeling and right ventricular hypertrophy. Frontiers Media S.A. 2023-02-13 /pmc/articles/PMC9969090/ /pubmed/36860846 http://dx.doi.org/10.3389/fimmu.2023.1105664 Text en Copyright © 2023 Bhattarai, He, Xu, Liu, Pan, Sun, Chen and Chen 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
Bhattarai, Umesh
He, Xiaochen
Xu, Rui
Liu, Xiaoguang
Pan, Lihong
Sun, Yuxiang
Chen, Jian-Xiong
Chen, Yingjie
IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression
title IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression
title_full IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression
title_fullStr IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression
title_full_unstemmed IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression
title_short IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression
title_sort il-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969090/
https://www.ncbi.nlm.nih.gov/pubmed/36860846
http://dx.doi.org/10.3389/fimmu.2023.1105664
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