Roxadustat markedly reduces myocardial ischemia reperfusion injury in mice

Hiroko Deguchi, Masataka Ikeda, Tomomi Ide, Tomonori Tadokoro, Soichiro Ikeda, Kosuke Okabe, Akihito Ishikita, Keita Saku, Shouji Matsushima, Hiroyuki Tsutsui

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1028-1033
Number of pages6
JournalCirculation Journal
Volume84
Issue number6
DOIs
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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