H-Ras Isoform Mediates Protection Against Pressure Overload-Induced Cardiac Dysfunction in Part Through Activation of AKT.
Circ Heart Fail
; 10(2)2017 Feb.
Article
en En
| MEDLINE
| ID: mdl-28193718
ABSTRACT
BACKGROUND:
In general, Ras proteins are thought to promote cardiac hypertrophy, an important risk factor for cardiovascular disease and heart failure. However, the contribution of different Ras isoforms has not been investigated. The objective of this study was to define the role of H- and K-Ras in modulating stress-induced myocardial hypertrophy and failure. METHODS ANDRESULTS:
We used H- and K-Ras gene knockout mice and subjected them to pressure overload to induce cardiac hypertrophy and dysfunction. We observed a worsened cardiac phenotype in Hras-/- mice, while outcomes were improved in Kras+/- mice. We also used a neonatal rat cardiomyocyte culture system to elucidate the mechanisms underlying these observations. Our findings demonstrate that H-Ras, but not K-Ras, promotes cardiomyocyte hypertrophy both in vivo and in vitro. This response was mediated in part through the phosphoinositide 3-kinase-AKT signaling pathway. Adeno-associated virus-mediated increase in AKT activation improved the cardiac function in pressure overloaded Hras null hearts in vivo. These findings further support engagement of the phosphoinositide 3-kinase-AKT signaling axis by H-Ras.CONCLUSIONS:
Taken together, these findings indicate that H- and K-Ras have divergent effects on cardiac hypertrophy and heart failure in response to pressure overload stress.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas p21(ras)
/
Proteínas Oncogénicas
/
Cardiomegalia
/
Proteínas ras
/
Miocitos Cardíacos
/
Proteínas Proto-Oncogénicas c-akt
/
Presión Arterial
/
Insuficiencia Cardíaca
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Circ Heart Fail
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2017
Tipo del documento:
Article