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Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes
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% accura...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978551/ https://www.ncbi.nlm.nih.gov/pubmed/31998851 http://dx.doi.org/10.1016/j.jacbts.2019.07.010 |
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author | 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 |
author_facet | 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 |
author_sort | Iborra-Egea, Oriol |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6978551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-69785512020-01-29 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 Transl Sci PRECLINICAL RESEARCH 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. Elsevier 2019-10-23 /pmc/articles/PMC6978551/ /pubmed/31998851 http://dx.doi.org/10.1016/j.jacbts.2019.07.010 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | PRECLINICAL RESEARCH 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 Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes |
title | Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes |
title_full | Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes |
title_fullStr | Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes |
title_full_unstemmed | Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes |
title_short | Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes |
title_sort | unraveling the molecular mechanism of action of empagliflozin in heart failure with reduced ejection fraction with or without diabetes |
topic | PRECLINICAL RESEARCH |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978551/ https://www.ncbi.nlm.nih.gov/pubmed/31998851 http://dx.doi.org/10.1016/j.jacbts.2019.07.010 |
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