Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction

Retinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have d...

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Autores principales:	Fabio Da Silva, Fariba Jian Motamedi, Lahiru Chamara Weerasinghe Arachchige, Amelie Tison, Stephen T Bradford, Jonathan Lefebvre, Pascal Dolle, Norbert B Ghyselinck, Kay D Wagner, Andreas Schedl
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	retinoic acid signaling heart development myocardial infarction Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/63c203ebcf0d472caf745a6f7dfa85c5
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spelling	oai:doaj.org-article:63c203ebcf0d472caf745a6f7dfa85c52021-11-25T10:22:59ZRetinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction10.7554/eLife.682802050-084Xe68280https://doaj.org/article/63c203ebcf0d472caf745a6f7dfa85c52021-10-01T00:00:00Zhttps://elifesciences.org/articles/68280https://doaj.org/toc/2050-084XRetinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line using CreERT2 technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of the Aldh1a1/a2/a3 genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals Tgm2 and Ace1, two genes with well-established links to cardiac repair, as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.Fabio Da SilvaFariba Jian MotamediLahiru Chamara Weerasinghe ArachchigeAmelie TisonStephen T BradfordJonathan LefebvrePascal DolleNorbert B GhyselinckKay D WagnerAndreas SchedleLife Sciences Publications Ltdarticleretinoic acid signalingheart developmentmyocardial infarctionMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	retinoic acid signaling heart development myocardial infarction Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	retinoic acid signaling heart development myocardial infarction Medicine R Science Q Biology (General) QH301-705.5 Fabio Da Silva Fariba Jian Motamedi Lahiru Chamara Weerasinghe Arachchige Amelie Tison Stephen T Bradford Jonathan Lefebvre Pascal Dolle Norbert B Ghyselinck Kay D Wagner Andreas Schedl Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
description	Retinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line using CreERT2 technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of the Aldh1a1/a2/a3 genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals Tgm2 and Ace1, two genes with well-established links to cardiac repair, as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.
format	article
author	Fabio Da Silva Fariba Jian Motamedi Lahiru Chamara Weerasinghe Arachchige Amelie Tison Stephen T Bradford Jonathan Lefebvre Pascal Dolle Norbert B Ghyselinck Kay D Wagner Andreas Schedl
author_facet	Fabio Da Silva Fariba Jian Motamedi Lahiru Chamara Weerasinghe Arachchige Amelie Tison Stephen T Bradford Jonathan Lefebvre Pascal Dolle Norbert B Ghyselinck Kay D Wagner Andreas Schedl
author_sort	Fabio Da Silva
title	Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
title_short	Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
title_full	Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
title_fullStr	Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
title_full_unstemmed	Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
title_sort	retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/63c203ebcf0d472caf745a6f7dfa85c5
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Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction

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