Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice

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  • Deguchi Hiroko
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Ikeda Masataka
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Ide Tomomi
    Department of Experimental and Clinical Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Tadokoro Tomonori
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Ikeda Soichiro
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Okabe Kosuke
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Ishikita Akihito
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Saku Keita
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University
  • Matsushima Shouji
    Department of Cardiovascular Medicine, Kyushu University Hospital
  • Tsutsui Hiroyuki
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University

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Abstract

<p>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.</p><p>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.</p><p>Conclusions:RXD pretreatment may be a novel strategy against I/R injury.</p>

Journal

  • Circulation Journal

    Circulation Journal 84 (6), 1028-1033, 2020-05-25

    The Japanese Circulation Society

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