Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3

Background Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular morbidity and mortality worldwide. Pyroptosis is a form of inflammatory cell death that plays a major role in the development and progression of cardiac injury in AMI. However, the underlying mechanisms for t...

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Autores principales:	Kang‐Zhen Zhang, Xi‐Yu Shen, Man Wang, Li Wang, Hui‐Xian Sun, Xiu‐Zhen Li, Jing‐Jing Huang, Xiao‐Qing Li, Cheng Wu, Can Zhao, Jia‐Li Liu, Xiang Lu, Wei Gao
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	acute myocardial infarction ischemia‐hypoxia NLRP3 pyroptosis retinol‐binding protein 4 Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/5473b889a34d4232b723804998bef6c1
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spelling	oai:doaj.org-article:5473b889a34d4232b723804998bef6c12021-11-16T10:22:44ZRetinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP310.1161/JAHA.121.0220112047-9980https://doaj.org/article/5473b889a34d4232b723804998bef6c12021-11-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.022011https://doaj.org/toc/2047-9980Background Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular morbidity and mortality worldwide. Pyroptosis is a form of inflammatory cell death that plays a major role in the development and progression of cardiac injury in AMI. However, the underlying mechanisms for the activation of pyroptosis during AMI are not fully elucidated. Methods and Results Here we show that RBP4 (retinol‐binding protein 4), a previous identified proinflammatory adipokine, was increased both in the myocardium of left anterior descending artery ligation‐induced AMI mouse model and in ischemia‐hypoxia‒induced cardiomyocyte injury model. The upregulated RBP4 may contribute to the activation of cardiomyocyte pyroptosis in AMI because overexpression of RBP4 activated NLRP3 (nucleotide‐binding oligomerization domain‐like receptor family pyrin domain‐containing 3) inflammasome, promoted the precursor cleavage of Caspase‐1, and subsequently induced GSDMD (gasdermin‐D)‐dependent pyroptosis. In contrast, knockdown of RBP4 alleviated ischemia‐hypoxia‒induced activation of NLRP3 inflammasome signaling and pyroptosis in cardiomyocytes. Mechanistically, coimmunoprecipitation assay showed that RBP4 interacted directly with NLRP3 in cardiomyocyte, while genetic knockdown or pharmacological inhibition of NLRP3 attenuated RBP4‐induced pyroptosis in cardiomyocytes. Finally, knockdown of RBP4 in heart decreased infarct size and protected against AMI‐induced pyroptosis and cardiac dysfunction in mice. Conclusions Taken together, these findings reveal RBP4 as a novel modulator promoting cardiomyocyte pyroptosis via interaction with NLRP3 in AMI. Therefore, targeting cardiac RBP4 might represent a viable strategy for the prevention of cardiac injury in patients with AMI.Kang‐Zhen ZhangXi‐Yu ShenMan WangLi WangHui‐Xian SunXiu‐Zhen LiJing‐Jing HuangXiao‐Qing LiCheng WuCan ZhaoJia‐Li LiuXiang LuWei GaoWileyarticleacute myocardial infarctionischemia‐hypoxiaNLRP3pyroptosisretinol‐binding protein 4Diseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute myocardial infarction ischemia‐hypoxia NLRP3 pyroptosis retinol‐binding protein 4 Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	acute myocardial infarction ischemia‐hypoxia NLRP3 pyroptosis retinol‐binding protein 4 Diseases of the circulatory (Cardiovascular) system RC666-701 Kang‐Zhen Zhang Xi‐Yu Shen Man Wang Li Wang Hui‐Xian Sun Xiu‐Zhen Li Jing‐Jing Huang Xiao‐Qing Li Cheng Wu Can Zhao Jia‐Li Liu Xiang Lu Wei Gao Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3
description	Background Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular morbidity and mortality worldwide. Pyroptosis is a form of inflammatory cell death that plays a major role in the development and progression of cardiac injury in AMI. However, the underlying mechanisms for the activation of pyroptosis during AMI are not fully elucidated. Methods and Results Here we show that RBP4 (retinol‐binding protein 4), a previous identified proinflammatory adipokine, was increased both in the myocardium of left anterior descending artery ligation‐induced AMI mouse model and in ischemia‐hypoxia‒induced cardiomyocyte injury model. The upregulated RBP4 may contribute to the activation of cardiomyocyte pyroptosis in AMI because overexpression of RBP4 activated NLRP3 (nucleotide‐binding oligomerization domain‐like receptor family pyrin domain‐containing 3) inflammasome, promoted the precursor cleavage of Caspase‐1, and subsequently induced GSDMD (gasdermin‐D)‐dependent pyroptosis. In contrast, knockdown of RBP4 alleviated ischemia‐hypoxia‒induced activation of NLRP3 inflammasome signaling and pyroptosis in cardiomyocytes. Mechanistically, coimmunoprecipitation assay showed that RBP4 interacted directly with NLRP3 in cardiomyocyte, while genetic knockdown or pharmacological inhibition of NLRP3 attenuated RBP4‐induced pyroptosis in cardiomyocytes. Finally, knockdown of RBP4 in heart decreased infarct size and protected against AMI‐induced pyroptosis and cardiac dysfunction in mice. Conclusions Taken together, these findings reveal RBP4 as a novel modulator promoting cardiomyocyte pyroptosis via interaction with NLRP3 in AMI. Therefore, targeting cardiac RBP4 might represent a viable strategy for the prevention of cardiac injury in patients with AMI.
format	article
author	Kang‐Zhen Zhang Xi‐Yu Shen Man Wang Li Wang Hui‐Xian Sun Xiu‐Zhen Li Jing‐Jing Huang Xiao‐Qing Li Cheng Wu Can Zhao Jia‐Li Liu Xiang Lu Wei Gao
author_facet	Kang‐Zhen Zhang Xi‐Yu Shen Man Wang Li Wang Hui‐Xian Sun Xiu‐Zhen Li Jing‐Jing Huang Xiao‐Qing Li Cheng Wu Can Zhao Jia‐Li Liu Xiang Lu Wei Gao
author_sort	Kang‐Zhen Zhang
title	Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3
title_short	Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3
title_full	Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3
title_fullStr	Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3
title_full_unstemmed	Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3
title_sort	retinol‐binding protein 4 promotes cardiac injury after myocardial infarction via inducing cardiomyocyte pyroptosis through an interaction with nlrp3
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/5473b889a34d4232b723804998bef6c1
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Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3

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