Pharmacological inhibition of GRK2 improves cardiac metabolism and function in experimental heart failure.
ESC Heart Fail
; 7(4): 1571-1584, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32352228
ABSTRACT
AIMS:
The effects of GRK2 inhibition on myocardial metabolism in heart failure (HF) are unchartered. In this work, we evaluated the impact of pharmacological inhibition of GRK2 by a cyclic peptide, C7, on metabolic, biochemical, and functional phenotypes in experimental HF. METHODS ANDRESULTS:
C7 was initially tested on adult mice ventricular myocyte from wild type and GRK2 myocardial deficient mice (GRK2-cKO), to assess the selectivity on GRK2 inhibition. Then, chronic infusion of 2 mg/kg/day of C7 was performed in HF mice with cryogenic myocardial infarction. Cardiac function in vivo was assessed by echocardiography and cardiac catheterization. Histological, biochemical, and metabolic studies were performed on heart samples at time points. C7 induces a significant increase of contractility in wild type but not in adult ventricle myocytes from GRK2-cKO mice, thus confirming C7 selectivity for GRK2. In HF mice, 4 weeks of treatment with C7 improved metabolic features, including mitochondrial organization and function, and restored the biochemical and contractile responses.CONCLUSIONS:
GRK2 is a critical molecule in the physiological regulation of cardiac metabolism. Its alterations in the failing heart can be pharmacologically targeted, leading to the correction of metabolic and functional abnormalities observed in HF.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Insuficiencia Cardíaca
/
Infarto del Miocardio
Límite:
Animals
Idioma:
En
Revista:
ESC Heart Fail
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia