Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure

Heat shock protein (HSP) 70 is a molecular chaperone that regulates protein structure in response to thermal stress. In addition, HSP70 is involved in post-translational modification and is related to the severity of some diseases. Here, we tested the functional relevance of long-lasting HSP70 expre...

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Autores principales:	Somy Yoon, Ulrich Gergs, Julie R. McMullen, Gwang Hyeon Eom
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	post-translational modification phosphorylation dilated cardiomyopathy heart failure HSP70 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c6ba76c1924f43beaa622dc1a06093ae
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spelling	oai:doaj.org-article:c6ba76c1924f43beaa622dc1a06093ae2021-11-25T17:12:23ZOverexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure10.3390/cells101131802073-4409https://doaj.org/article/c6ba76c1924f43beaa622dc1a06093ae2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3180https://doaj.org/toc/2073-4409Heat shock protein (HSP) 70 is a molecular chaperone that regulates protein structure in response to thermal stress. In addition, HSP70 is involved in post-translational modification and is related to the severity of some diseases. Here, we tested the functional relevance of long-lasting HSP70 expression in a model of nonischemic heart failure using protein phosphatase 2 catalytic subunit A (PP2CA)-expressing transgenic mice. These transgenic mice, with cardiac-specific overexpression of PP2CA, abruptly died after 12 weeks of postnatal life. Serial echocardiograms to assess cardiac function revealed that the ejection fraction (EF) was gradually decreased in transgenic PP2CA (TgPP2CA) mice. In addition, PP2CA expression exacerbated systolic dysfunction and LV dilatation, with free wall thinning, which are indicators of fatal dilated cardiomyopathy. Interestingly, simultaneous expression of HSP70 in double transgenic mice (dTg) significantly improved the dilated cardiomyopathy phenotype of TgPP2CA mice. We observed better survival, preserved EF, reduced chamber enlargement, and suppression of free wall thinning. In the proposed molecular mechanism, HSP70 preferentially regulates the phosphorylation of AKT. Phosphorylation of AKT was significantly reduced in TgPP2CA mice but was not significantly lower in dTg mice. Signal crosstalk between AKT and its substrates, in association with HSP70, might be a useful intervention for patients with nonischemic heart failure to suppress cardiac remodeling and improve survival.Somy YoonUlrich GergsJulie R. McMullenGwang Hyeon EomMDPI AGarticlepost-translational modificationphosphorylationdilated cardiomyopathyheart failureHSP70Biology (General)QH301-705.5ENCells, Vol 10, Iss 3180, p 3180 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	post-translational modification phosphorylation dilated cardiomyopathy heart failure HSP70 Biology (General) QH301-705.5
spellingShingle	post-translational modification phosphorylation dilated cardiomyopathy heart failure HSP70 Biology (General) QH301-705.5 Somy Yoon Ulrich Gergs Julie R. McMullen Gwang Hyeon Eom Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure
description	Heat shock protein (HSP) 70 is a molecular chaperone that regulates protein structure in response to thermal stress. In addition, HSP70 is involved in post-translational modification and is related to the severity of some diseases. Here, we tested the functional relevance of long-lasting HSP70 expression in a model of nonischemic heart failure using protein phosphatase 2 catalytic subunit A (PP2CA)-expressing transgenic mice. These transgenic mice, with cardiac-specific overexpression of PP2CA, abruptly died after 12 weeks of postnatal life. Serial echocardiograms to assess cardiac function revealed that the ejection fraction (EF) was gradually decreased in transgenic PP2CA (TgPP2CA) mice. In addition, PP2CA expression exacerbated systolic dysfunction and LV dilatation, with free wall thinning, which are indicators of fatal dilated cardiomyopathy. Interestingly, simultaneous expression of HSP70 in double transgenic mice (dTg) significantly improved the dilated cardiomyopathy phenotype of TgPP2CA mice. We observed better survival, preserved EF, reduced chamber enlargement, and suppression of free wall thinning. In the proposed molecular mechanism, HSP70 preferentially regulates the phosphorylation of AKT. Phosphorylation of AKT was significantly reduced in TgPP2CA mice but was not significantly lower in dTg mice. Signal crosstalk between AKT and its substrates, in association with HSP70, might be a useful intervention for patients with nonischemic heart failure to suppress cardiac remodeling and improve survival.
format	article
author	Somy Yoon Ulrich Gergs Julie R. McMullen Gwang Hyeon Eom
author_facet	Somy Yoon Ulrich Gergs Julie R. McMullen Gwang Hyeon Eom
author_sort	Somy Yoon
title	Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure
title_short	Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure
title_full	Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure
title_fullStr	Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure
title_full_unstemmed	Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure
title_sort	overexpression of heat shock protein 70 improves cardiac remodeling and survival in protein phosphatase 2a-expressing transgenic mice with chronic heart failure
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c6ba76c1924f43beaa622dc1a06093ae
work_keys_str_mv	AT somyyoon overexpressionofheatshockprotein70improvescardiacremodelingandsurvivalinproteinphosphatase2aexpressingtransgenicmicewithchronicheartfailure AT ulrichgergs overexpressionofheatshockprotein70improvescardiacremodelingandsurvivalinproteinphosphatase2aexpressingtransgenicmicewithchronicheartfailure AT juliermcmullen overexpressionofheatshockprotein70improvescardiacremodelingandsurvivalinproteinphosphatase2aexpressingtransgenicmicewithchronicheartfailure AT gwanghyeoneom overexpressionofheatshockprotein70improvescardiacremodelingandsurvivalinproteinphosphatase2aexpressingtransgenicmicewithchronicheartfailure
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Overexpression of Heat Shock Protein 70 Improves Cardiac Remodeling and Survival in Protein Phosphatase 2A-Expressing Transgenic Mice with Chronic Heart Failure

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