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.
CITATION STYLE
Deguchi, H., Ikeda, M., Ide, T., Tadokoro, T., Ikeda, S., Okabe, K., … Tsutsui, H. (2020). Roxadustat markedly reduces myocardial ischemia reperfusion injury in mice. Circulation Journal, 84(6), 1028–1033. https://doi.org/10.1253/circj.CJ-19-1039
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