A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction

Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) orchestrates cellular...

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Autores principales:	Darko Maric, Aleksandra Paterek, Marion Delaunay, Irene Pérez López, Miroslav Arambasic, Dario Diviani
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	A-kinase-anchoring protein (AKAP) protein kinase A cAMP cardiomyocyte myocardial infarction scaffolding proteins Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6aad7f067fb14eaca2000c7eb0abff59
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spelling	oai:doaj.org-article:6aad7f067fb14eaca2000c7eb0abff592021-11-25T17:08:10ZA-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction10.3390/cells101128612073-4409https://doaj.org/article/6aad7f067fb14eaca2000c7eb0abff592021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2861https://doaj.org/toc/2073-4409Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) orchestrates cellular processes favoring cardioprotection in infarcted hearts. Induction of AKAP2 knockout (KO) in cardiomyocytes of adult mice increases infarct size and exacerbates cardiac dysfunction after MI, as visualized by increased left ventricular dilation and reduced fractional shortening and ejection fraction. In cardiomyocytes, AKAP2 forms a signaling complex with PKA and the steroid receptor co-activator 3 (Src3). Upon activation of cAMP signaling, the AKAP2/PKA/Src3 complex favors PKA-mediated phosphorylation and activation of estrogen receptor α (ERα). This results in the upregulation of ER-dependent genes involved in protection against apoptosis and angiogenesis, including Bcl2 and the vascular endothelial growth factor a (VEGFa). In line with these findings, cardiomyocyte-specific AKAP2 KO reduces Bcl2 and VEGFa expression, increases myocardial apoptosis and impairs the formation of new blood vessels in infarcted hearts. Collectively, our findings suggest that AKAP2 organizes a transcriptional complex that mediates pro-angiogenic and anti-apoptotic responses that protect infarcted hearts.Darko MaricAleksandra PaterekMarion DelaunayIrene Pérez LópezMiroslav ArambasicDario DivianiMDPI AGarticleA-kinase-anchoring protein (AKAP)protein kinase AcAMPcardiomyocytemyocardial infarctionscaffolding proteinsBiology (General)QH301-705.5ENCells, Vol 10, Iss 2861, p 2861 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	A-kinase-anchoring protein (AKAP) protein kinase A cAMP cardiomyocyte myocardial infarction scaffolding proteins Biology (General) QH301-705.5
spellingShingle	A-kinase-anchoring protein (AKAP) protein kinase A cAMP cardiomyocyte myocardial infarction scaffolding proteins Biology (General) QH301-705.5 Darko Maric Aleksandra Paterek Marion Delaunay Irene Pérez López Miroslav Arambasic Dario Diviani A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction
description	Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) orchestrates cellular processes favoring cardioprotection in infarcted hearts. Induction of AKAP2 knockout (KO) in cardiomyocytes of adult mice increases infarct size and exacerbates cardiac dysfunction after MI, as visualized by increased left ventricular dilation and reduced fractional shortening and ejection fraction. In cardiomyocytes, AKAP2 forms a signaling complex with PKA and the steroid receptor co-activator 3 (Src3). Upon activation of cAMP signaling, the AKAP2/PKA/Src3 complex favors PKA-mediated phosphorylation and activation of estrogen receptor α (ERα). This results in the upregulation of ER-dependent genes involved in protection against apoptosis and angiogenesis, including Bcl2 and the vascular endothelial growth factor a (VEGFa). In line with these findings, cardiomyocyte-specific AKAP2 KO reduces Bcl2 and VEGFa expression, increases myocardial apoptosis and impairs the formation of new blood vessels in infarcted hearts. Collectively, our findings suggest that AKAP2 organizes a transcriptional complex that mediates pro-angiogenic and anti-apoptotic responses that protect infarcted hearts.
format	article
author	Darko Maric Aleksandra Paterek Marion Delaunay Irene Pérez López Miroslav Arambasic Dario Diviani
author_facet	Darko Maric Aleksandra Paterek Marion Delaunay Irene Pérez López Miroslav Arambasic Dario Diviani
author_sort	Darko Maric
title	A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction
title_short	A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction
title_full	A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction
title_fullStr	A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction
title_full_unstemmed	A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction
title_sort	a-kinase anchoring protein 2 promotes protection against myocardial infarction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6aad7f067fb14eaca2000c7eb0abff59
work_keys_str_mv	AT darkomaric akinaseanchoringprotein2promotesprotectionagainstmyocardialinfarction AT aleksandrapaterek akinaseanchoringprotein2promotesprotectionagainstmyocardialinfarction AT mariondelaunay akinaseanchoringprotein2promotesprotectionagainstmyocardialinfarction AT ireneperezlopez akinaseanchoringprotein2promotesprotectionagainstmyocardialinfarction AT miroslavarambasic akinaseanchoringprotein2promotesprotectionagainstmyocardialinfarction AT dariodiviani akinaseanchoringprotein2promotesprotectionagainstmyocardialinfarction
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A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction

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