Decoding empagliflozin's molecular mechanism of action in heart failure with preserved ejection fraction using artificial intelligence.
Artificial Intelligence
Benzhydryl Compounds
/ pharmacology
Glucosides
/ pharmacology
Heart Failure
/ drug therapy
Humans
Models, Cardiovascular
Myocardium
/ metabolism
Sodium-Glucose Transporter 2
/ metabolism
Sodium-Glucose Transporter 2 Inhibitors
/ pharmacology
Sodium-Hydrogen Exchanger 1
/ metabolism
Stroke Volume
/ drug effects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 06 2021
08 06 2021
Historique:
received:
10
03
2021
accepted:
27
05
2021
entrez:
9
6
2021
pubmed:
10
6
2021
medline:
21
10
2021
Statut:
epublish
Résumé
The use of sodium-glucose co-transporter 2 inhibitors to treat heart failure with preserved ejection fraction (HFpEF) is under investigation in ongoing clinical trials, but the exact mechanism of action is unclear. Here we aimed to use artificial intelligence (AI) to characterize the mechanism of action of empagliflozin in HFpEF at the molecular level. We retrieved information regarding HFpEF pathophysiological motifs and differentially expressed genes/proteins, together with empagliflozin target information and bioflags, from specialized publicly available databases. Artificial neural networks and deep learning AI were used to model the molecular effects of empagliflozin in HFpEF. The model predicted that empagliflozin could reverse 59% of the protein alterations found in HFpEF. The effects of empagliflozin in HFpEF appeared to be predominantly mediated by inhibition of NHE1 (Na
Identifiants
pubmed: 34103605
doi: 10.1038/s41598-021-91546-z
pii: 10.1038/s41598-021-91546-z
pmc: PMC8187349
doi:
Substances chimiques
Benzhydryl Compounds
0
Glucosides
0
SLC5A2 protein, human
0
SLC9A1 protein, human
0
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
Sodium-Hydrogen Exchanger 1
0
empagliflozin
HDC1R2M35U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12025Références
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