Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice

被引：51
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
收藏
页码：1028 / 1033
页数：6
相关论文
共 20 条
  • [1] HIF Hydroxylase Pathways in Cardiovascular Physiology and Medicine
    Bishop, Tammie
    Ratcliffe, Peter J.
    [J]. CIRCULATION RESEARCH, 2015, 117 (01) : 65 - 79
  • [2] Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1α
    Cai, Zheqing
    Zhong, Hua
    Bosch-Marce, Marta
    Fox-Talbot, Karen
    Wang, Lei
    Wei, Chiming
    Trush, Michael A.
    Semenza, Gregg L.
    [J]. CARDIOVASCULAR RESEARCH, 2008, 77 (03) : 463 - 470
  • [3] Recombinant mitochondrial transcription factor A protein inhibits nuclear factor of activated T cells signaling and attenuates pathological hypertrophy of cardiac myocytes
    Fujino, Takeo
    Ide, Tomomi
    Yoshida, Masayoshi
    Onitsuka, Ken
    Tanaka, Atsushi
    Hata, Yuko
    Nishida, Motohiro
    Takehara, Takako
    Kanemaru, Takaaki
    Kitajima, Naoyuki
    Takazaki, Shinya
    Kurose, Hitoshi
    Kang, Dongchon
    Sunagawa, Kenji
    [J]. MITOCHONDRION, 2012, 12 (04) : 449 - 458
  • [4] Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery
    Hausenloy, D. J.
    Candilio, L.
    Evans, R.
    Ariti, C.
    Jenkins, D. P.
    Kolvekar, S.
    Knight, R.
    Kunst, G.
    Laing, C.
    Nicholas, J.
    Pepper, J.
    Robertson, S.
    Xenou, M.
    Clayton, T.
    Yellon, D. M.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (15) : 1408 - 1417
  • [5] Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial
    Hausenloy, Derek J.
    Mwamure, Peter K.
    Venugopal, Vinod
    Harris, Joanne
    Barnard, Matthew
    Grundy, Ernie
    Ashley, Elizabeth
    Vichare, Sanjeev
    Di Salvo, Carmelo
    Kolvekar, Shyam
    Hayward, Martin
    Keogh, Bruce
    MacAllister, Raymond J.
    Yellon, Derek M.
    [J]. LANCET, 2007, 370 (9587) : 575 - 579
  • [6] Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial
    Hausenloy, Derek J.
    Kharbanda, Rajesh K.
    Moller, Ulla Kristine
    Ramlall, Manish
    Aaroe, Jens
    Butler, Robert
    Bulluck, Heerajnarain
    Clayton, Tim
    Dana, Ali
    Dodd, Matthew
    Engstrom, Thomas
    Evans, Richard
    Lassen, Jens Flensted
    Christensen, Erika Frischknecht
    Manuel Garcia-Ruiz, Jose
    Gorog, Diana A.
    Hjort, Jakob
    Houghton, Richard F.
    Ibanez, Borja
    Knight, Rosemary
    Lippert, Freddy K.
    Lonborg, Jacob T.
    Maeng, Michael
    Milasinovic, Dejan
    More, Ranjit
    Nicholas, Jennifer M.
    Jensen, Lisette Okkels
    Perkins, Alexander
    Radovanovic, Nebojsa
    Rakhit, Roby D.
    Ravkilde, Jan
    Ryding, Alisdair D.
    Schmidt, Michael R.
    Riddervold, Ingunn Skogstad
    Sorensen, Henrik Toft
    Stankovic, Goran
    Varma, Madhusudhan
    Webb, Ian
    Terkelsen, Christian Juhl
    Greenwood, John P.
    Yellon, Derek M.
    Botker, Hans Erik
    [J]. LANCET, 2019, 394 (10207) : 1415 - 1424
  • [7] Cardioprotection Techniques: Preconditioning, Postconditioning and Remote Con-ditioning (Basic Science)
    Hausenloy, Derek J.
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2013, 19 (25) : 4544 - 4563
  • [8] Risk factors for congestive heart failure in US men and women -: NHANES I epidemiologic follow-up study
    He, J
    Ogden, LG
    Bazzano, LA
    Vupputuri, S
    Loria, C
    Whelton, PK
    [J]. ARCHIVES OF INTERNAL MEDICINE, 2001, 161 (07) : 996 - 1002
  • [9] Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway
    Kaelin, William G., Jr.
    Ratcliffe, Peter J.
    [J]. MOLECULAR CELL, 2008, 30 (04) : 393 - 402
  • [10] The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    Maxwell, PH
    Wiesener, MS
    Chang, GW
    Clifford, SC
    Vaux, EC
    Cockman, ME
    Wykoff, CC
    Pugh, CW
    Maher, ER
    Ratcliffe, PJ
    [J]. NATURE, 1999, 399 (6733) : 271 - 275
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