Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats

Background. Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elic...

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Autores principales:	Yang Zhao, Huaxin Sun, Kai Li, Luxiang Shang, Xiaoyan Liang, Hang Yang, Zhenyu Dong, Jiasuoer Xiaokereti, Shuai Shang, Qina Zhou, Xianhui Zhou, Ling Zhang, Yanmei Lu, Baopeng Tang
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Pathology RB1-214
Acceso en línea:	https://doaj.org/article/65caad9132c841f395ebe47d1b26b1eb
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spelling	oai:doaj.org-article:65caad9132c841f395ebe47d1b26b1eb2021-11-29T00:56:53ZCholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats1466-186110.1155/2021/4504431https://doaj.org/article/65caad9132c841f395ebe47d1b26b1eb2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/4504431https://doaj.org/toc/1466-1861Background. Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elicitation prevents ventricular remodeling in CHF by protecting myocardial mitochondrial injuries and its underlying mechanisms. Methods and Results. CHF models were established by ligation of anterior descending artery for 5 weeks. Postoperative survival rats were assigned into 5 groups: the sham group (sham, n=10), CHF group (CHF, n=11), Vag group (CHF+vagotomy, n=10), PNU group (CHF+PNU-282987 for 4 weeks, n=11), and Vag+PNU group (CHF+vagotomy+PNU-282987 for 4 weeks, n=10). The antiventricular remodeling effect of cholinergic elicitation was evaluated in vivo, and H9C2 cells were selected for the TNF-α gradient stimulation experiment in vitro. In vivo, CAP agitated by PNU-282987 alleviated the left ventricular dysfunction and inhibited the energy metabolism remodeling. Further, cholinergic elicitation increased myocardium ATP levels and reduced systemic inflammation. CAP induction alleviates macrophage infiltration and cardiac fibrosis, of which the effect is counteracted by vagotomy. Myocardial mitochondrial injuries were ameliorated by CAP activation, including the reserved ultrastructural integrity, declining ROS overload, reduced myocardial apoptosis, and enhanced mitochondrial fusion. In vitro, TNF-α intervention significantly exacerbated the mitochondrial damage in H9C2 cells. Conclusion. CAP elicitation effectively improves ischemic ventricular remodeling by suppressing systemic and cardiac inflammatory response, attenuating cardiac fibrosis and potentially alleviating the mitochondrial dysfunction linked to hyperinflammation reaction.Yang ZhaoHuaxin SunKai LiLuxiang ShangXiaoyan LiangHang YangZhenyu DongJiasuoer XiaokeretiShuai ShangQina ZhouXianhui ZhouLing ZhangYanmei LuBaopeng TangHindawi LimitedarticlePathologyRB1-214ENMediators of Inflammation, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214
spellingShingle	Pathology RB1-214 Yang Zhao Huaxin Sun Kai Li Luxiang Shang Xiaoyan Liang Hang Yang Zhenyu Dong Jiasuoer Xiaokereti Shuai Shang Qina Zhou Xianhui Zhou Ling Zhang Yanmei Lu Baopeng Tang Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats
description	Background. Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elicitation prevents ventricular remodeling in CHF by protecting myocardial mitochondrial injuries and its underlying mechanisms. Methods and Results. CHF models were established by ligation of anterior descending artery for 5 weeks. Postoperative survival rats were assigned into 5 groups: the sham group (sham, n=10), CHF group (CHF, n=11), Vag group (CHF+vagotomy, n=10), PNU group (CHF+PNU-282987 for 4 weeks, n=11), and Vag+PNU group (CHF+vagotomy+PNU-282987 for 4 weeks, n=10). The antiventricular remodeling effect of cholinergic elicitation was evaluated in vivo, and H9C2 cells were selected for the TNF-α gradient stimulation experiment in vitro. In vivo, CAP agitated by PNU-282987 alleviated the left ventricular dysfunction and inhibited the energy metabolism remodeling. Further, cholinergic elicitation increased myocardium ATP levels and reduced systemic inflammation. CAP induction alleviates macrophage infiltration and cardiac fibrosis, of which the effect is counteracted by vagotomy. Myocardial mitochondrial injuries were ameliorated by CAP activation, including the reserved ultrastructural integrity, declining ROS overload, reduced myocardial apoptosis, and enhanced mitochondrial fusion. In vitro, TNF-α intervention significantly exacerbated the mitochondrial damage in H9C2 cells. Conclusion. CAP elicitation effectively improves ischemic ventricular remodeling by suppressing systemic and cardiac inflammatory response, attenuating cardiac fibrosis and potentially alleviating the mitochondrial dysfunction linked to hyperinflammation reaction.
format	article
author	Yang Zhao Huaxin Sun Kai Li Luxiang Shang Xiaoyan Liang Hang Yang Zhenyu Dong Jiasuoer Xiaokereti Shuai Shang Qina Zhou Xianhui Zhou Ling Zhang Yanmei Lu Baopeng Tang
author_facet	Yang Zhao Huaxin Sun Kai Li Luxiang Shang Xiaoyan Liang Hang Yang Zhenyu Dong Jiasuoer Xiaokereti Shuai Shang Qina Zhou Xianhui Zhou Ling Zhang Yanmei Lu Baopeng Tang
author_sort	Yang Zhao
title	Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats
title_short	Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats
title_full	Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats
title_fullStr	Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats
title_full_unstemmed	Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats
title_sort	cholinergic elicitation prevents ventricular remodeling via alleviations of myocardial mitochondrial injury linked to inflammation in ischemia-induced chronic heart failure rats
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/65caad9132c841f395ebe47d1b26b1eb
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Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats

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