Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes

Oriol Iborra-Egea; Evelyn  Santiago-Vacas; Salva Yurista; Joseph Lupón; Milton Packer; Stephane Heymans; Faiez Zannad; Javed Butler; Domingo Pascal-Figal; Antonio Lax; Julio Núñez; Rudolf Boer, de; Antonio Bayés-Genís

doi:10.1016/j.jacbts.2019.07.010

Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes

Oriol Iborra-Egea, Evelyn Santiago-Vacas, Salva Yurista, Joseph Lupón, Milton Packer, Stephane Heymans, Faiez Zannad, Javed Butler, Domingo Pascal-Figal, Antonio Lax, Julio Núñez, Rudolf Boer, de, Antonio Bayés-Genís

Cardiovasculair Centrum

Onderzoeksoutput: Article › Academic › peer review

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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-1 (NHE1) 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.

Originele taal-2	English
Aantal pagina's	10
Tijdschrift	JACC: Basic to Translational Science
DOI's	https://doi.org/10.1016/j.jacbts.2019.07.010
Status	Published - okt.-2019

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10.1016/j.jacbts.2019.07.010Licentie: CC BY-NC-ND

Unraveling the Molecular Mechanism ofAction of Empagliflozin in Heart FailureWith Reduced Ejection FractionWith or Without DiabetesFinal publisher's version, 1,07 MBLicentie: CC BY-NC-ND

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Iborra-Egea, O., Santiago-Vacas, E., Yurista, S., Lupón, J., Packer, M., Heymans, S., Zannad, F., Butler, J., Pascal-Figal, D., Lax, A., Núñez, J., Boer, de, R., & Bayés-Genís, A. (2019). Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes. JACC: Basic to Translational Science. https://doi.org/10.1016/j.jacbts.2019.07.010

@article{75a11e9c1ce94887a01e5d409225c33c,

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-1 (NHE1) 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.",

author = "Oriol Iborra-Egea and Evelyn Santiago-Vacas and Salva Yurista and Joseph Lup{\'o}n and Milton Packer and Stephane Heymans and Faiez Zannad and Javed Butler and Domingo Pascal-Figal and Antonio Lax and Julio N{\'u}{\~n}ez and {Boer, de}, Rudolf and Antonio Bay{\'e}s-Gen{\'i}s",

year = "2019",

month = oct,

doi = "10.1016/j.jacbts.2019.07.010",

language = "English",

journal = "JACC: Basic to Translational Science",

publisher = "Elsevier",

}

Iborra-Egea, O, Santiago-Vacas, E, Yurista, S, Lupón, J, Packer, M, Heymans, S, Zannad, F, Butler, J, Pascal-Figal, D, Lax, A, Núñez, J, Boer, de, R & Bayés-Genís, A 2019, 'Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes', JACC: Basic to Translational Science. https://doi.org/10.1016/j.jacbts.2019.07.010

TY - JOUR

T1 - Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes

AU - Iborra-Egea, Oriol

AU - Santiago-Vacas, Evelyn

AU - Yurista, Salva

AU - Lupón, Joseph

AU - Packer, Milton

AU - Heymans, Stephane

AU - Zannad, Faiez

AU - Butler, Javed

AU - Pascal-Figal, Domingo

AU - Lax, Antonio

AU - Núñez, Julio

AU - Boer, de, Rudolf

AU - Bayés-Genís, Antonio

PY - 2019/10

Y1 - 2019/10

N2 - 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-1 (NHE1) 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.

AB - 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-1 (NHE1) 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.

UR - http://basictranslational.onlinejacc.org/content/early/2019/10/16/j.jacbts.2019.07.010

U2 - 10.1016/j.jacbts.2019.07.010

DO - 10.1016/j.jacbts.2019.07.010

M3 - Article

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

ER -

Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes

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