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

Oriol Iborra-Egea, Evelyn Santiago-Vacas, Salva R. Yurista, Josep Lupón, Milton Packer, Stephane Heymans, Faiez Zannad, Javed Butler, Domingo Pascual-Figal, Antonio Lax, Julio Núñez, Rudolf A. de Boer, Antoni Bayés-Genís*

*Autor corresponent d’aquest treball

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74 Cites (Scopus)

Resum

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.

Idioma originalAnglès nord-americà
Pàgines (de-a)831-840
Nombre de pàgines10
RevistaJACC: Basic to Translational Science
Volum4
Número7
DOIs
Estat de la publicacióPublicada - de nov. 2019

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