Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenolinduced cell death and heart failure.
Int J Mol Med
; 51(2)2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36579657
ABSTRACT
CXCR4 is a seventransmembranespanning Gicoupled receptor for the SDF1 chemokine and plays a critical role in cardiovascular development and postinjury repair. However, the specific role of CXCR4 in cardiomyocytes is incompletely understood. It was hypothesized that CXCR4 activation in cardiomyocytes antagonizes ßadrenoceptor/Gs signalinginduced cardiac dysfunction. Cardiomyocytespecific CXCR4 knockout (CXCR4CMKO) mice were generated by crossing CXCR4fl/fl and MHCCre+/ mice. Their cardiac structure and function in the basal state are equivalent to that of the control MHCCre+/ littermates until at least 4 months old. However, following continuous subcutaneous administration of isoproterenol (Iso) via an osmotic minipump, the ventricular myocardial contractility, dilation, cardiomyocyte apoptosis, and interstitial fibrosis are worse in CXCR4CMKO mice than in MHCCre+/ littermates. In the cultured H9C2 cardiomyocytes, SDF1 treatment markedly attenuated Isoinduced apoptosis and reduction in phosphoAkt, and this protective effect was lost by knockdown of CXCR4 or by cotreatment with Gi inhibitors. In conclusion, CXCR4 promotes cardiomyocyte survival and heart function during ßadrenergic stress.
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Base de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
/
Insuficiência Cardíaca
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article