Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy

Abstract We recently reported the reduced ATP-sensitive potassium (KATP) channel activities in the transgenic mouse heart overexpressing the vascular type KATP channel pore-forming subunit (Kir6.1). Although dysfunction of cardiac KATP channel has been nominated as a cause of cardiomyopathy in human...

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Autores principales:	Yasuhiro Watanabe, Takashi Kishimoto, Takashi Miki, Susumu Seino, Haruaki Nakaya, Akio Matsumoto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6102e71ff39e47bda2eca019553263e0
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spelling	oai:doaj.org-article:6102e71ff39e47bda2eca019553263e02021-12-02T15:09:04ZEctopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy10.1038/s41598-018-30175-52045-2322https://doaj.org/article/6102e71ff39e47bda2eca019553263e02018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30175-5https://doaj.org/toc/2045-2322Abstract We recently reported the reduced ATP-sensitive potassium (KATP) channel activities in the transgenic mouse heart overexpressing the vascular type KATP channel pore-forming subunit (Kir6.1). Although dysfunction of cardiac KATP channel has been nominated as a cause of cardiomyopathy in human, these transgenic mice looked normal as wild-type (WT) during the experiment period (~20 weeks). Extended observation period revealed unexpected deaths beginning from 30 weeks and about 50% of the transgenic mice died by 55 weeks. Surface ECG recordings from the transgenic mice at rest demonstrated the normal sinus rhythm and the regular ECG complex as well as the control WT mice except for prolonged QT interval. However, the stress ECG test with noradrenaline revealed abnormal intraventricular conduction delay and arrhythmogeneity in the transgenic mouse. Fibrotic changes in the heart tissue were remarkable in aged transgenic mice, and the cardiac fibrosis developed progressively at least from the age of 30 weeks. Gene expression analyses revealed the differentiation of cardiac fibroblasts to myofibroblasts with elevated cytokine expressions was initiated way in advance before the fibrotic changes and the upregulation of BNP in the ventricle. In sum, Kir6.1TG mice provide an electro-pathological disease concept originated from KATP channel dysfunction.Yasuhiro WatanabeTakashi KishimotoTakashi MikiSusumu SeinoHaruaki NakayaAkio MatsumotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yasuhiro Watanabe Takashi Kishimoto Takashi Miki Susumu Seino Haruaki Nakaya Akio Matsumoto Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy
description	Abstract We recently reported the reduced ATP-sensitive potassium (KATP) channel activities in the transgenic mouse heart overexpressing the vascular type KATP channel pore-forming subunit (Kir6.1). Although dysfunction of cardiac KATP channel has been nominated as a cause of cardiomyopathy in human, these transgenic mice looked normal as wild-type (WT) during the experiment period (~20 weeks). Extended observation period revealed unexpected deaths beginning from 30 weeks and about 50% of the transgenic mice died by 55 weeks. Surface ECG recordings from the transgenic mice at rest demonstrated the normal sinus rhythm and the regular ECG complex as well as the control WT mice except for prolonged QT interval. However, the stress ECG test with noradrenaline revealed abnormal intraventricular conduction delay and arrhythmogeneity in the transgenic mouse. Fibrotic changes in the heart tissue were remarkable in aged transgenic mice, and the cardiac fibrosis developed progressively at least from the age of 30 weeks. Gene expression analyses revealed the differentiation of cardiac fibroblasts to myofibroblasts with elevated cytokine expressions was initiated way in advance before the fibrotic changes and the upregulation of BNP in the ventricle. In sum, Kir6.1TG mice provide an electro-pathological disease concept originated from KATP channel dysfunction.
format	article
author	Yasuhiro Watanabe Takashi Kishimoto Takashi Miki Susumu Seino Haruaki Nakaya Akio Matsumoto
author_facet	Yasuhiro Watanabe Takashi Kishimoto Takashi Miki Susumu Seino Haruaki Nakaya Akio Matsumoto
author_sort	Yasuhiro Watanabe
title	Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy
title_short	Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy
title_full	Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy
title_fullStr	Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy
title_full_unstemmed	Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy
title_sort	ectopic overexpression of kir6.1 in the mouse heart impacts on the life expectancy
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6102e71ff39e47bda2eca019553263e0
work_keys_str_mv	AT yasuhirowatanabe ectopicoverexpressionofkir61inthemouseheartimpactsonthelifeexpectancy AT takashikishimoto ectopicoverexpressionofkir61inthemouseheartimpactsonthelifeexpectancy AT takashimiki ectopicoverexpressionofkir61inthemouseheartimpactsonthelifeexpectancy AT susumuseino ectopicoverexpressionofkir61inthemouseheartimpactsonthelifeexpectancy AT haruakinakaya ectopicoverexpressionofkir61inthemouseheartimpactsonthelifeexpectancy AT akiomatsumoto ectopicoverexpressionofkir61inthemouseheartimpactsonthelifeexpectancy
_version_	1718387941063000064

Ectopic overexpression of Kir6.1 in the mouse heart impacts on the life expectancy

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