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

This article has now been updated. Please use the final version.

Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice
Hiroko DeguchiMasataka IkedaTomomi IdeTomonori TadokoroSoichiro IkedaKosuke OkabeAkihito IshikitaKeita SakuShouji MatsushimaHiroyuki Tsutsui
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JOURNAL FREE ACCESS FULL-TEXT HTML Advance online publication

Article ID: CJ-19-1039

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Abstract

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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