Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice.
Animals
Cell Respiration
/ drug effects
Cells, Cultured
Disease Models, Animal
Enzyme Inhibitors
/ pharmacology
Glycine
/ analogs & derivatives
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Hypoxia-Inducible Factor-Proline Dioxygenases
/ antagonists & inhibitors
Isoquinolines
/ pharmacology
Male
Mice, Inbred C57BL
Myocardial Infarction
/ metabolism
Myocardial Reperfusion Injury
/ metabolism
Myocytes, Cardiac
/ drug effects
Signal Transduction
Hypoxia-inducible factor-1α (Hif-1α)
Ischemia/reperfusion injury
Roxadustat
Journal
Circulation journal : official journal of the Japanese Circulation Society
ISSN: 1347-4820
Titre abrégé: Circ J
Pays: Japan
ID NLM: 101137683
Informations de publication
Date de publication:
25 05 2020
25 05 2020
Historique:
pubmed:
28
3
2020
medline:
15
12
2020
entrez:
28
3
2020
Statut:
ppublish
Résumé
Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1α (Hif-1α) is a key molecule in IPC, and roxadustat (RXD), a first-in-class prolyl hydroxylase domain-containing protein inhibitor, has been recently developed to treat anemia in patients with chronic kidney disease. Thus, we investigated whether RXD pretreatment protects against I/R injury.Methods and Results:RXD pretreatment markedly reduced the infarct size and suppressed plasma creatinine kinase activity in a murine I/R model. Analysis of oxygen metabolism showed that RXD could produce ischemic tolerance by shifting metabolism from aerobic to anaerobic respiration. RXD pretreatment may be a novel strategy against I/R injury.
Sections du résumé
BACKGROUND
Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1α (Hif-1α) is a key molecule in IPC, and roxadustat (RXD), a first-in-class prolyl hydroxylase domain-containing protein inhibitor, has been recently developed to treat anemia in patients with chronic kidney disease. Thus, we investigated whether RXD pretreatment protects against I/R injury.Methods and Results:RXD pretreatment markedly reduced the infarct size and suppressed plasma creatinine kinase activity in a murine I/R model. Analysis of oxygen metabolism showed that RXD could produce ischemic tolerance by shifting metabolism from aerobic to anaerobic respiration.
CONCLUSIONS
RXD pretreatment may be a novel strategy against I/R injury.
Identifiants
pubmed: 32213720
doi: 10.1253/circj.CJ-19-1039
doi:
Substances chimiques
Enzyme Inhibitors
0
Hif1a protein, mouse
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Isoquinolines
0
Hypoxia-Inducible Factor-Proline Dioxygenases
EC 1.14.11.29
Glycine
TE7660XO1C
roxadustat
X3O30D9YMX
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1028-1033Commentaires et corrections
Type : CommentIn