@article{b4b24235ef16423a972bb5679816e98c,
title = "Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes",
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 = "empagliflozin, heart failure, machine learning",
author = "Oriol Iborra-Egea and Evelyn Santiago-Vacas and Yurista, {Salva R.} and Josep Lup{\'o}n and Milton Packer and Stephane Heymans and Faiez Zannad and Javed Butler and Domingo Pascual-Figal and Antonio Lax and Julio N{\'u}{\~n}ez and {de Boer}, {Rudolf A.} and Antoni Bay{\'e}s-Gen{\'i}s",
note = "Funding Information: The authors thank Boehringer Ingelheim for providing animal control subjects and chow containing empagliflozin. Dr. Yurista is supported by Indonesia Endowment Fund for Education grant LPDP 20150722083422. Dr. Packer is a consultant with Abbvie, Amgen, Akcea, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Gilead, Johnson and Johnson, NovoNordisk, Pfizer, Sanofi, Synthetic Biologics, Relypsa, and Theravance. Dr. Zannad is a member of the Boehringer Ingelheim steering committee; and is a consultant for AstraZeneca, Mundipharma, NovoNordisk, and Merck. Dr. Butler is a consultant with Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, BerlinCures, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiocell, Corvidia, CVRx, G3 Pharmaceutical, Innolife, Janssen, Lantheus, LinaNova, Luitpold, Medscape, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, StealthPeptide, SC Pharma, V-Wave Limited, Vifor, and ZS Pharma. Dr. N??ez has received speaker fees from Boehringer Ingelheim. Dr. De Boer holds equity in scPharmaceuticals; has received honoraria from Mandalmed, Novartis, and Servier; and has received research support through his institution from AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Roche, Trevena, and ThermoFisher GmbH. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2019",
month = nov,
doi = "10.1016/j.jacbts.2019.07.010",
language = "Ingl{\'e}s estadounidense",
volume = "4",
pages = "831--840",
journal = "JACC: Basic to Translational Science",
issn = "2452-302X",
publisher = "Elsevier Inc.",
number = "7",
}