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oai:repisalud.isciii.es:20.500.12105/96582024-09-27T09:48:21Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Iborra-Egea, Oriol author Santiago-Vacas, Evelyn author Yurista, Salva R author Lupón, Josep author Packer, Milton author Heymans, Stephane author Zannad, Faiez author Butler, Javed author Pascual-Figal, Domingo A author Lax, Antonio author Núñez, Julio author de Boer, Rudolf A author Bayes-Genis, Antoni author 2019-11 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. JACC Basic Transl Sci. 2019; 4(7):831-840 10.1016/j.jacbts.2019.07.010 2452-302X 2452-302X JACC. Basic to translational science 31998851 http://hdl.handle.net/20.500.12105/9658 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 Unraveling the Molecular Mechanism of Action of Empagliflozin in Heart Failure With Reduced Ejection Fraction With or Without Diabetes