Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice

被引：52

作者：

Deguchi, Hiroko ^{[1
]}

Ikeda, Masataka ^{[1
]}

Ide, Tomomi ^{[2
]}

Tadokoro, Tomonori ^{[1
]}

Ikeda, Soichiro ^{[1
]}

Okabe, Kosuke ^{[1
]}

Ishikita, Akihito ^{[1
]}

Saku, Keita ^{[1
]}

Matsushima, Shouji ^{[3
]}

Tsutsui, Hiroyuki ^{[1
]}

机构：

[1] Kyushu Univ, Fac Med Sci, Dept Cardiovasc Med, Fukuoka, Japan

[2] Kyushu Univ, Fac Med Sci, Dept Expt & Clin Cardiovasc Med, Fukuoka, Japan

[3] Kyushu Univ Hosp, Dept Cardiovasc Med, Fukuoka, Japan

来源：

CIRCULATION JOURNAL | 2020年 / 84卷 / 06期

关键词：

Hypoxia-inducible factor-1 alpha (Hif-1 alpha); Ischemia/reperfusion injury; Roxadustat; HYPOXIA-INDUCIBLE FACTORS; CARDIOPROTECTION; PHYSIOLOGY;

D O I：

10.1253/circj.CJ-19-1039

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1 alpha (Hif-1 alpha) 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.

引用

页码：1028 / 1033

页数：6

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