Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling

Abstract GTP cyclohydrolase 1 (GCH1) and its product tetrahydrobiopterin play crucial roles in cardiovascular health and disease, yet the exact regulation and role of GCH1 in adverse cardiac remodeling after myocardial infarction are still enigmatic. Here we report that cardiac GCH1 is degraded in r...

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Autores principales:	Yanan Liu, Shelley L. Baumgardt, Juan Fang, Yang Shi, Shigang Qiao, Zeljko J. Bosnjak, Jeannette Vásquez-Vivar, Zhengyuan Xia, David C. Warltier, Judy R. Kersten, Zhi-Dong Ge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/10546a57160b4846a85f06d91c1197c8
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spelling	oai:doaj.org-article:10546a57160b4846a85f06d91c1197c82021-12-02T12:32:44ZTransgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling10.1038/s41598-017-03234-62045-2322https://doaj.org/article/10546a57160b4846a85f06d91c1197c82017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03234-6https://doaj.org/toc/2045-2322Abstract GTP cyclohydrolase 1 (GCH1) and its product tetrahydrobiopterin play crucial roles in cardiovascular health and disease, yet the exact regulation and role of GCH1 in adverse cardiac remodeling after myocardial infarction are still enigmatic. Here we report that cardiac GCH1 is degraded in remodeled hearts after myocardial infarction, concomitant with increases in the thickness of interventricular septum, interstitial fibrosis, and phosphorylated p38 mitogen-activated protein kinase and decreases in left ventricular anterior wall thickness, cardiac contractility, tetrahydrobiopterin, the dimers of nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and the expression of sarcoplasmic reticulum Ca2+ handling proteins. Intriguingly, transgenic overexpression of GCH1 in cardiomyocytes reduces the thickness of interventricular septum and interstitial fibrosis and increases anterior wall thickness and cardiac contractility after infarction. Moreover, we show that GCH1 overexpression decreases phosphorylated p38 mitogen-activated protein kinase and elevates tetrahydrobiopterin levels, the dimerization and phosphorylation of neuronal nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and sarcoplasmic reticulum Ca2+ handling proteins in post-infarction remodeled hearts. Our results indicate that the pivotal role of GCH1 overexpression in post-infarction cardiac remodeling is attributable to preservation of neuronal nitric oxide synthase and sarcoplasmic reticulum Ca2+ handling proteins, and identify a new therapeutic target for cardiac remodeling after infarction.Yanan LiuShelley L. BaumgardtJuan FangYang ShiShigang QiaoZeljko J. BosnjakJeannette Vásquez-VivarZhengyuan XiaDavid C. WarltierJudy R. KerstenZhi-Dong GeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yanan Liu Shelley L. Baumgardt Juan Fang Yang Shi Shigang Qiao Zeljko J. Bosnjak Jeannette Vásquez-Vivar Zhengyuan Xia David C. Warltier Judy R. Kersten Zhi-Dong Ge Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling
description	Abstract GTP cyclohydrolase 1 (GCH1) and its product tetrahydrobiopterin play crucial roles in cardiovascular health and disease, yet the exact regulation and role of GCH1 in adverse cardiac remodeling after myocardial infarction are still enigmatic. Here we report that cardiac GCH1 is degraded in remodeled hearts after myocardial infarction, concomitant with increases in the thickness of interventricular septum, interstitial fibrosis, and phosphorylated p38 mitogen-activated protein kinase and decreases in left ventricular anterior wall thickness, cardiac contractility, tetrahydrobiopterin, the dimers of nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and the expression of sarcoplasmic reticulum Ca2+ handling proteins. Intriguingly, transgenic overexpression of GCH1 in cardiomyocytes reduces the thickness of interventricular septum and interstitial fibrosis and increases anterior wall thickness and cardiac contractility after infarction. Moreover, we show that GCH1 overexpression decreases phosphorylated p38 mitogen-activated protein kinase and elevates tetrahydrobiopterin levels, the dimerization and phosphorylation of neuronal nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and sarcoplasmic reticulum Ca2+ handling proteins in post-infarction remodeled hearts. Our results indicate that the pivotal role of GCH1 overexpression in post-infarction cardiac remodeling is attributable to preservation of neuronal nitric oxide synthase and sarcoplasmic reticulum Ca2+ handling proteins, and identify a new therapeutic target for cardiac remodeling after infarction.
format	article
author	Yanan Liu Shelley L. Baumgardt Juan Fang Yang Shi Shigang Qiao Zeljko J. Bosnjak Jeannette Vásquez-Vivar Zhengyuan Xia David C. Warltier Judy R. Kersten Zhi-Dong Ge
author_facet	Yanan Liu Shelley L. Baumgardt Juan Fang Yang Shi Shigang Qiao Zeljko J. Bosnjak Jeannette Vásquez-Vivar Zhengyuan Xia David C. Warltier Judy R. Kersten Zhi-Dong Ge
author_sort	Yanan Liu
title	Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling
title_short	Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling
title_full	Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling
title_fullStr	Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling
title_full_unstemmed	Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling
title_sort	transgenic overexpression of gtp cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/10546a57160b4846a85f06d91c1197c8
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Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling

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