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...

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Detalhes bibliográficos
Autores: Iborra Egea, Oriol|||0000-0002-7280-859X, Santiago Vacas, Evelyn|||0000-0001-7511-406X, Yurista, Salva R., Lupón, Josep|||0000-0002-5601-9611, Packer, Milton, Heymans, Stephane, Zannad, Faiez, Butler, Javed|||0000-0001-7683-4720, Pascual-Figal, DA.|||0000-0002-4993-9540, Lax, Antonio, Núñez, Julio|||0000-0003-1672-7119, de Boer, Rudolf A.., Bayés-Genís, Antoni|||0000-0002-3044-197X
Tipo de documento: artigo
Data de publicação:2019
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:226228
Acesso em linha:https://ddd.uab.cat/record/226228
https://dx.doi.org/urn:doi:10.1016/j.jacbts.2019.07.010
Access Level:Acceso aberto
Palavra-chave:Empagliflozin
Heart failure
Machine learning
Descrição
Resumo: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.

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