Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes.
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
empagliflozin
heart failure
machine learning
Journal
JACC. Basic to translational science
ISSN: 2452-302X
Titre abrégé: JACC Basic Transl Sci
Pays: United States
ID NLM: 101677259
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
20
05
2019
revised:
09
07
2019
accepted:
09
07
2019
entrez:
31
1
2020
pubmed:
31
1
2020
medline:
31
1
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31998851
doi: 10.1016/j.jacbts.2019.07.010
pii: S2452-302X(19)30224-4
pmc: PMC6978551
doi:
Types de publication
Journal Article
Langues
eng
Pagination
831-840Informations de copyright
© 2019 The Authors.
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