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

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;
jacc basic to translational science 2019 Vol. 4 pp. 831-840
282
iborraegea2019unravelingjacc

Abstract

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.

Keywords

Machine learning empagliflozin heart failure ann, artificial neural network dm, diabetes mellitus hf, heart failure hfref, hf with reduced ejection fraction mi-hf, post-infarct heart failure nhe, sodium-hydrogen exchanger rnaseq, rna sequencing sglt2i, sodium-glucose co-transporter 2 inhibitor

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DOI:
10.1016/j.jacbts.2019.07.010

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ID: 88060
Ref Key: iborraegea2019unravelingjacc
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