Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice

  • Circ J. 2020 May 25;84(6):1028-1033. doi: 10.1253/circj.CJ-19-1039.
Hiroko Deguchi  1 ,  Masataka Ikeda  1 ,  Tomomi Ide  2 ,  Tomonori Tadokoro  1 ,  Soichiro Ikeda  1 ,  Kosuke Okabe  1 ,  Akihito Ishikita  1 ,  Keita Saku  1 ,  Shouji Matsushima  3 ,  Hiroyuki Tsutsui  1
Affiliations
  • 1. Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University.
  • 2. Department of Experimental and Clinical Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University.
  • 3. Department of Cardiovascular Medicine, Kyushu University Hospital.
PMID: 32213720 DOI: 10.1253/circj.CJ-19-1039
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.

Keywords
Hypoxia-inducible factor-1α (Hif-1α); Ischemia/reperfusion injury; Roxadustat.
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