Angiotensin receptor-neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction.
Clin Exp Pharmacol Physiol
; 49(8): 848-857, 2022 08.
Article
en En
| MEDLINE
| ID: mdl-35596518
ABSTRACT
LCZ696, an angiotensin receptor-neprilysin inhibitor, has shown promising clinical efficacy in patients with heart failure (HF) with reduced ejection fraction. However, its potential effects on heart failure with preserved ejection fraction (HFpEF) are still not fully understood. We evaluated the effect of LCZ696 on HFpEF in transverse aortic constriction mice and compared it with the effect of the angiotensin receptor blocker, valsartan. We found that LCZ696 improved cardiac diastolic function by reducing ventricular hypertrophy and fibrosis in mice with overload-induced diastolic dysfunction. In addition, there was superior inhibition of LCZ696 than stand-alone valsartan. As a potential underlying mechanism, we demonstrated that LCZ696 behaves as a potent suppressor of calcium-mediated calcineurin-nuclear factor of activated T cells (NFAT) signalling transduction pathways. Hence, we demonstrated the protective effects of LCZ696 in overload-induced HFpEF and provided a pharmaceutical therapeutic strategy for related diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Volumen Sistólico
/
Compuestos de Bifenilo
/
Neprilisina
/
Cardiomegalia
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Antagonistas de Receptores de Angiotensina
/
Valsartán
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Aminobutiratos
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Insuficiencia Cardíaca
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China