A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction.

Details

Serval ID
serval:BIB_03C005C7A0F6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction.
Journal
Cells
Author(s)
Maric D., Paterek A., Delaunay M., López I.P., Arambasic M., Diviani D.
ISSN
2073-4409 (Electronic)
ISSN-L
2073-4409
Publication state
Published
Issued date
23/10/2021
Peer-reviewed
Oui
Volume
10
Number
11
Pages
2861
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
A-kinase-anchoring protein (AKAP), cAMP, cardiomyocyte, myocardial infarction, protein kinase A, scaffolding proteins
Pubmed
Web of science
Open Access
Yes
Create date
03/12/2021 11:51
Last modification date
20/07/2022 6:38
Usage data