Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis

Myocardial injury caused by ischemia-reperfusion is the main pathological manifestation of coronary artery disease (CAD), which is characterized by high mortality and morbidity. Thus, there’s an urgent need to develop efficacious strategies and elucidate the underlying mechanisms to prevent or allev...

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Autores principales:	Qiong Jiang, Xianfeng Dong, Danqing Hu, Lejun Chen, Yukun Luo
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	myocardial ischemia-reperfusion injury pyroptosis aquaporin 4 (aqp4) Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/7b997ce7cc244d70b5c467a7d04d3ce6
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spelling	oai:doaj.org-article:7b997ce7cc244d70b5c467a7d04d3ce62021-11-04T15:51:54ZAquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis2165-59792165-598710.1080/21655979.2021.1992332https://doaj.org/article/7b997ce7cc244d70b5c467a7d04d3ce62021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1992332https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Myocardial injury caused by ischemia-reperfusion is the main pathological manifestation of coronary artery disease (CAD), which is characterized by high mortality and morbidity. Thus, there’s an urgent need to develop efficacious strategies and elucidate the underlying mechanisms to prevent or alleviate myocardial ischemia-reperfusion injury to improve the clinical outcomes in patients. In this study, we took advantage of a typical myocardial cell line of mice (HL-1) and cultured with or without an aquaporin 4 inhibitor (TGN-20 denoted as AQP4i) under normal conditions (NC), ischemia (IS) and ischemia reperfusion (IR), respectively. The cytomorphology, ultrastructure, cell vitality and expression pattern of apoptotic proteins were verified with scanning electron microscope (SEM), immunofluorescence staining, flow cytometry, quantitative real-time PCR and western-blotting analysis, respectively. HL-1 under IS or IR condition revealed higher expression of Aquaporin 4 (Aqp4) compared to the NC group, whereas showed similarity in cytomorphology and ultrastructure. Aqp4 inhibition was sufficient to improve the apoptotic cells in HL-1 while showed minimal effects to the other cellular vitality. Furthermore, the expression pattern of apoptotic proteins and anti-apoptotic proteins together with proinflammatory factors in HL-1 was effectively rescued by Aqp4i treatment both at the mRNA level and protein level. Ischemia and ischemia reperfusion caused higher expression of Aqp4 and resultant increase of cardiomyocyte pyroptosis. Myocardial ischemia-reperfusion injury of HL-1 was effectively alleviated by Aqp4 and pyroptosis inhibition. Our findings provided new references for myocardial ischemia-reperfusion injury management via targeting Aqp4-mediated pyroptosis of cardiomyocyte.Qiong JiangXianfeng DongDanqing HuLejun ChenYukun LuoTaylor & Francis Grouparticlemyocardial ischemia-reperfusion injurypyroptosisaquaporin 4 (aqp4)BiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 1, Pp 9021-9030 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myocardial ischemia-reperfusion injury pyroptosis aquaporin 4 (aqp4) Biotechnology TP248.13-248.65
spellingShingle	myocardial ischemia-reperfusion injury pyroptosis aquaporin 4 (aqp4) Biotechnology TP248.13-248.65 Qiong Jiang Xianfeng Dong Danqing Hu Lejun Chen Yukun Luo Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis
description	Myocardial injury caused by ischemia-reperfusion is the main pathological manifestation of coronary artery disease (CAD), which is characterized by high mortality and morbidity. Thus, there’s an urgent need to develop efficacious strategies and elucidate the underlying mechanisms to prevent or alleviate myocardial ischemia-reperfusion injury to improve the clinical outcomes in patients. In this study, we took advantage of a typical myocardial cell line of mice (HL-1) and cultured with or without an aquaporin 4 inhibitor (TGN-20 denoted as AQP4i) under normal conditions (NC), ischemia (IS) and ischemia reperfusion (IR), respectively. The cytomorphology, ultrastructure, cell vitality and expression pattern of apoptotic proteins were verified with scanning electron microscope (SEM), immunofluorescence staining, flow cytometry, quantitative real-time PCR and western-blotting analysis, respectively. HL-1 under IS or IR condition revealed higher expression of Aquaporin 4 (Aqp4) compared to the NC group, whereas showed similarity in cytomorphology and ultrastructure. Aqp4 inhibition was sufficient to improve the apoptotic cells in HL-1 while showed minimal effects to the other cellular vitality. Furthermore, the expression pattern of apoptotic proteins and anti-apoptotic proteins together with proinflammatory factors in HL-1 was effectively rescued by Aqp4i treatment both at the mRNA level and protein level. Ischemia and ischemia reperfusion caused higher expression of Aqp4 and resultant increase of cardiomyocyte pyroptosis. Myocardial ischemia-reperfusion injury of HL-1 was effectively alleviated by Aqp4 and pyroptosis inhibition. Our findings provided new references for myocardial ischemia-reperfusion injury management via targeting Aqp4-mediated pyroptosis of cardiomyocyte.
format	article
author	Qiong Jiang Xianfeng Dong Danqing Hu Lejun Chen Yukun Luo
author_facet	Qiong Jiang Xianfeng Dong Danqing Hu Lejun Chen Yukun Luo
author_sort	Qiong Jiang
title	Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis
title_short	Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis
title_full	Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis
title_fullStr	Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis
title_full_unstemmed	Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis
title_sort	aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/7b997ce7cc244d70b5c467a7d04d3ce6
work_keys_str_mv	AT qiongjiang aquaporin4inhibitionalleviatesmyocardialischemiareperfusioninjurybyrestrainingcardiomyocytepyroptosis AT xianfengdong aquaporin4inhibitionalleviatesmyocardialischemiareperfusioninjurybyrestrainingcardiomyocytepyroptosis AT danqinghu aquaporin4inhibitionalleviatesmyocardialischemiareperfusioninjurybyrestrainingcardiomyocytepyroptosis AT lejunchen aquaporin4inhibitionalleviatesmyocardialischemiareperfusioninjurybyrestrainingcardiomyocytepyroptosis AT yukunluo aquaporin4inhibitionalleviatesmyocardialischemiareperfusioninjurybyrestrainingcardiomyocytepyroptosis
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Aquaporin 4 inhibition alleviates myocardial ischemia-reperfusion injury by restraining cardiomyocyte pyroptosis

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