A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction

Autor: Marion Delaunay, Darko Maric, Dario Diviani, Irene Pérez López, Aleksandra Paterek, Miroslav Arambasic
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Vascular Endothelial Growth Factor A
Angiogenesis
Myocardial Infarction
A Kinase Anchor Proteins
cardiomyocyte
Apoptosis
Receptors
G-Protein-Coupled
Nuclear Receptor Coactivator 3
Rats
Sprague-Dawley
Electrocardiography
0302 clinical medicine
Myocytes
Cardiac
Myocardial infarction
Biology (General)
Phosphorylation
Cardioprotection
A-kinase-anchoring protein (AKAP)
Mice
Knockout
0303 health sciences
Ejection fraction
General Medicine
Cell biology
Up-Regulation
Vascular endothelial growth factor A
Proto-Oncogene Proteins c-bcl-2
Receptors
Estrogen
030220 oncology & carcinogenesis
cAMP
myocardial infarction
protein kinase A
scaffolding proteins
Signal Transduction
Cardiotonic Agents
QH301-705.5
Article
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
RNA
Messenger
Protein kinase A
030304 developmental biology
business.industry
Myocardium
Membrane Proteins
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Fibrosis
Mice
Inbred C57BL
Animals
Newborn
Heart failure
business
Gene Deletion
Zdroj: Cells
Cells; Volume 10; Issue 11; Pages: 2861
Cells, Vol 10, Iss 2861, p 2861 (2021)
Cells, vol. 10, no. 11, pp. 2861
ISSN: 2073-4409
Popis: 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.
Databáze: OpenAIRE
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