Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843

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Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice
Hiroko DeguchiMasataka IkedaTomomi IdeTomonori TadokoroSoichiro IkedaKosuke OkabeAkihito IshikitaKeita SakuShouji MatsushimaHiroyuki Tsutsui
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論文ID: CJ-19-1039

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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.

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