Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes

The mechanism of action of empagliflozin in heart failure with reduced ejection fraction (HFrEF) was deciphered using deep learning in silico analyses together with in vivo validation. The most robust mechanism of action involved the sodium-hydrogen exchanger (NHE)-1 co-transporter with 94.7% accura...

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Detalles Bibliográficos
Autores principales: Iborra-Egea, Oriol, Santiago-Vacas, Evelyn, Yurista, Salva R., Lupón, Josep, Packer, Milton, Heymans, Stephane, Zannad, Faiez, Butler, Javed, Pascual-Figal, Domingo, Lax, Antonio, Núñez, Julio, de Boer, Rudolf A., Bayés-Genís, Antoni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
PRECLINICAL RESEARCH
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978551/
https://www.ncbi.nlm.nih.gov/pubmed/31998851
http://dx.doi.org/10.1016/j.jacbts.2019.07.010
Descripción
Sumario:The mechanism of action of empagliflozin in heart failure with reduced ejection fraction (HFrEF) was deciphered using deep learning in silico analyses together with in vivo validation. The most robust mechanism of action involved the sodium-hydrogen exchanger (NHE)-1 co-transporter with 94.7% accuracy, which was similar for diabetics and nondiabetics. Notably, direct NHE1 blockade by empagliflozin ameliorated cardiomyocyte cell death by restoring expression of X-linked inhibitor of apoptosis (XIAP) and baculoviral IAP repeat-containing protein 5 (BIRC5). These results were independent of diabetes mellitus comorbidity, suggesting that empagliflozin may emerge as a new treatment in HFrEF.

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