Publication:
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 Diabete.pdf(1.08 MB)
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Date
2019-10
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Authors
Iborra Egea, Oriol ; Santiago Vacas, Evelyn ; Yurista, Salva ; Lupon, Josep ; Packer, Milton ; Heymans, Stephane ; Pascual Figal, Domingo A. ; Lax PĂ©rez, Antonio Manuel ; Bayes Genis, Antoni
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Publisher
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Medicina
DOI
10.1016/j.jacbts.2019.07.010
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info:eu-repo/semantics/article
Description
Abstract
he 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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Citation
JACC Basic Transl Sci. 2019 Oct 23 4(7):831-840.doi: 10.1016/j.jacbts.2019.07.010.
URI
http://hdl.handle.net/10201/137594
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