著者
Hiroko Deguchi Masataka Ikeda Tomomi Ide Tomonori Tadokoro Soichiro Ikeda Kosuke Okabe Akihito Ishikita Keita Saku Shouji Matsushima Hiroyuki Tsutsui
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-19-1039, (Released:2020-03-24)
参考文献数
20
被引用文献数
2 36

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.
著者
Hiroko Deguchi Masataka Ikeda Tomomi Ide Tomonori Tadokoro Soichiro Ikeda Kosuke Okabe Akihito Ishikita Keita Saku Shouji Matsushima Hiroyuki Tsutsui
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.84, no.6, pp.1028-1033, 2020-05-25 (Released:2020-05-25)
参考文献数
20
被引用文献数
9 36

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.