Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

<h4>Aims</h4>It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo.<h4>Methods and results</h4>We generated a cardiac-specific CARP-overexpre...

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Autores principales:	Yao Song, Jialin Xu, Yanfeng Li, Chunshi Jia, Xiaowei Ma, Lei Zhang, Xiaojie Xie, Yong Zhang, Xiang Gao, Youyi Zhang, Dahai Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f37027918784749a6e1a03c0d897066
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spelling	oai:doaj.org-article:1f37027918784749a6e1a03c0d8970662021-11-18T08:06:20ZCardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.1932-620310.1371/journal.pone.0050436https://doaj.org/article/1f37027918784749a6e1a03c0d8970662012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23227174/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims</h4>It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo.<h4>Methods and results</h4>We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis.<h4>Conclusion</h4>CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.Yao SongJialin XuYanfeng LiChunshi JiaXiaowei MaLei ZhangXiaojie XieYong ZhangXiang GaoYouyi ZhangDahai ZhuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50436 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yao Song Jialin Xu Yanfeng Li Chunshi Jia Xiaowei Ma Lei Zhang Xiaojie Xie Yong Zhang Xiang Gao Youyi Zhang Dahai Zhu Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
description	<h4>Aims</h4>It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo.<h4>Methods and results</h4>We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis.<h4>Conclusion</h4>CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.
format	article
author	Yao Song Jialin Xu Yanfeng Li Chunshi Jia Xiaowei Ma Lei Zhang Xiaojie Xie Yong Zhang Xiang Gao Youyi Zhang Dahai Zhu
author_facet	Yao Song Jialin Xu Yanfeng Li Chunshi Jia Xiaowei Ma Lei Zhang Xiaojie Xie Yong Zhang Xiang Gao Youyi Zhang Dahai Zhu
author_sort	Yao Song
title	Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
title_short	Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
title_full	Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
title_fullStr	Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
title_full_unstemmed	Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
title_sort	cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of erk1/2 and tgf-β signaling pathways.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1f37027918784749a6e1a03c0d897066
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Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

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