Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction

Juanjuan Lyu,1 Jia Huang,2,3 Jin Wu,1 Tao Yu,3,4 Xinchuan Wei,2,3 Qian Lei2,3 1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Sichuan Provincial People’s Hospital, Un...

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Autores principales:	Lyu J, Huang J, Wu J, Yu T, Wei X, Lei Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	myocardial infarction ventricular arrhythmias macrophage migration inhibitory factor inflammatory mediators sympathetic nerve Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/eb42a5ecb47c4e3384424ca7e5c0aa54
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spelling	oai:doaj.org-article:eb42a5ecb47c4e3384424ca7e5c0aa542021-12-02T18:13:26ZLack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction1178-7031https://doaj.org/article/eb42a5ecb47c4e3384424ca7e5c0aa542021-04-01T00:00:00Zhttps://www.dovepress.com/lack-of-macrophage-migration-inhibitory-factor-reduces-susceptibility--peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Juanjuan Lyu,1 Jia Huang,2,3 Jin Wu,1 Tao Yu,3,4 Xinchuan Wei,2,3 Qian Lei2,3 1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 3Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, People’s Republic of China; 4Department of Cardiac Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of ChinaCorrespondence: Qian Lei Email leiqianggh@163.comBackground: Macrophages are involved in inflammatory responses and play a crucial role in aggravating ventricular arrhythmias (VAs) after myocardial infarction (MI). Macrophage migration inhibitory factor (MIF) participates in inflammatory responses during acute MI. In the present study, we hypothesized that knockout (KO) of MIF may prevent VAs during the acute phase of MI by inhibiting macrophage-derived pro-inflammatory mediators.Methods and Results: We demonstrated that MIF-KO mice in a mouse model of MI exhibited a significant decrease in susceptibility to VAs both in vivo (84.6% vs 40.7%, P < 0.05) and ex vivo (86.7% vs 40.0%, P < 0.05) at day 3 after MI compared with that in wild-type (WT) mice. Both WT and MIF-KO mice presented similar left ventricular contractility, peri-infarct myocardial fibrosis and sympathetic reinnervation, and circulating and local norepinephrine levels during the acute phase of MI. Meanwhile, MIF-KO mice had inhibited macrophage aggregation, alleviated connexin 43 (Cx43) redistribution, and reduced level of pro-inflammatory mediators, including tumor necrosis factor-α and interleukin-1β (P < 0.05) at day 3 after MI. The differences in susceptibility to VAs, expression of pro-inflammatory mediators, and Cx43 redistribution after MI between WT and MIF-KO mice disappeared by macrophage depletion with clodronate liposomes in both groups. Furthermore, the pro-inflammatory activity of cultured peritoneal macrophages was inhibited by MIF deficiency and recovered with replenishment of exogenous MIF in vitro.Conclusion: In conclusion, we found that lack of MIF reduced the susceptibility to VAs in mouse heart during the acute phase of MI by inhibiting pro-inflammatory activity of macrophages and improving gap-junction and electrical remodeling.Keywords: myocardial infarction, ventricular arrhythmias, macrophage migration inhibitory factor, inflammatory mediators, sympathetic nerveLyu JHuang JWu JYu TWei XLei QDove Medical Pressarticlemyocardial infarctionventricular arrhythmiasmacrophage migration inhibitory factorinflammatory mediatorssympathetic nervePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 1297-1311 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myocardial infarction ventricular arrhythmias macrophage migration inhibitory factor inflammatory mediators sympathetic nerve Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	myocardial infarction ventricular arrhythmias macrophage migration inhibitory factor inflammatory mediators sympathetic nerve Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Lyu J Huang J Wu J Yu T Wei X Lei Q Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction
description	Juanjuan Lyu,1 Jia Huang,2,3 Jin Wu,1 Tao Yu,3,4 Xinchuan Wei,2,3 Qian Lei2,3 1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 3Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, People’s Republic of China; 4Department of Cardiac Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of ChinaCorrespondence: Qian Lei Email leiqianggh@163.comBackground: Macrophages are involved in inflammatory responses and play a crucial role in aggravating ventricular arrhythmias (VAs) after myocardial infarction (MI). Macrophage migration inhibitory factor (MIF) participates in inflammatory responses during acute MI. In the present study, we hypothesized that knockout (KO) of MIF may prevent VAs during the acute phase of MI by inhibiting macrophage-derived pro-inflammatory mediators.Methods and Results: We demonstrated that MIF-KO mice in a mouse model of MI exhibited a significant decrease in susceptibility to VAs both in vivo (84.6% vs 40.7%, P < 0.05) and ex vivo (86.7% vs 40.0%, P < 0.05) at day 3 after MI compared with that in wild-type (WT) mice. Both WT and MIF-KO mice presented similar left ventricular contractility, peri-infarct myocardial fibrosis and sympathetic reinnervation, and circulating and local norepinephrine levels during the acute phase of MI. Meanwhile, MIF-KO mice had inhibited macrophage aggregation, alleviated connexin 43 (Cx43) redistribution, and reduced level of pro-inflammatory mediators, including tumor necrosis factor-α and interleukin-1β (P < 0.05) at day 3 after MI. The differences in susceptibility to VAs, expression of pro-inflammatory mediators, and Cx43 redistribution after MI between WT and MIF-KO mice disappeared by macrophage depletion with clodronate liposomes in both groups. Furthermore, the pro-inflammatory activity of cultured peritoneal macrophages was inhibited by MIF deficiency and recovered with replenishment of exogenous MIF in vitro.Conclusion: In conclusion, we found that lack of MIF reduced the susceptibility to VAs in mouse heart during the acute phase of MI by inhibiting pro-inflammatory activity of macrophages and improving gap-junction and electrical remodeling.Keywords: myocardial infarction, ventricular arrhythmias, macrophage migration inhibitory factor, inflammatory mediators, sympathetic nerve
format	article
author	Lyu J Huang J Wu J Yu T Wei X Lei Q
author_facet	Lyu J Huang J Wu J Yu T Wei X Lei Q
author_sort	Lyu J
title	Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction
title_short	Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction
title_full	Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction
title_fullStr	Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction
title_full_unstemmed	Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction
title_sort	lack of macrophage migration inhibitory factor reduces susceptibility to ventricular arrhythmias during the acute phase of myocardial infarction
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/eb42a5ecb47c4e3384424ca7e5c0aa54
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Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction

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