The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model

被引:87
|
作者
Dare, Anna J. [1 ,2 ]
Logan, Angela [1 ,2 ]
Prime, Tracy A. [1 ,2 ]
Rogatti, Sebastian [1 ,2 ]
Goddard, Martin [3 ]
Bolton, Eleanor M. [2 ,4 ]
Bradley, J. Andrew [2 ,4 ]
Pettigrew, Gavin J. [2 ,4 ]
Murphy, Michael P. [1 ,2 ]
Saeb-Parsy, Kourosh [2 ,4 ]
机构
[1] Univ Cambridge, MRC, Mitochondrial Biol Unit, Cambridge, England
[2] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England
[3] Papworth Hosp Natl Hlth Serv Fdn Trust, Cambridge, England
[4] Univ Cambridge, Dept Surg, Cambridge, England
来源
JOURNAL OF HEART AND LUNG TRANSPLANTATION | 2015年 / 34卷 / 11期
基金
英国医学研究理事会;
关键词
ischemia; reperfusion; transplantation; mitochondria-targeted anti-oxidants; MitoQ; CARDIAC COLD ISCHEMIA; TRIPHENYLPHOSPHONIUM CATIONS; PERMEABILITY TRANSITION; LUNG TRANSPLANTATION; GRAFT-SURVIVAL; REJECTION; DISEASE; PATHWAYS; CELLS; H2O2;
D O I
10.1016/j.healun.2015.05.007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND: Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model. METHODS: Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating Score, and inflammatory markers. 120 minutes or 24 hours post-transplant. RESULTS: MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondria! DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient. CONCLUSIONS: IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.
引用
收藏
页码:1471 / 1480
页数:10
相关论文
共 50 条
  • [41] A novel murine model of cyclical cutaneous ischemia-reperfusion injury
    Reid, RR
    Sull, AC
    Mogford, JE
    Roy, N
    Mustoe, TA
    JOURNAL OF SURGICAL RESEARCH, 2004, 116 (01) : 172 - 180
  • [42] A noninvasive murine model of hind limb ischemia-reperfusion injury
    Bonheur, JA
    Albadawi, H
    Patton, GM
    Watkins, MT
    JOURNAL OF SURGICAL RESEARCH, 2004, 116 (01) : 55 - 63
  • [43] BERGAMOT JUICE EXTRACT EXERTS A NOTABLE ANTI-INFLAMMATORY AND ANTI-OXIDANT EFFECT IN A MURINE MODEL OF INTESTINAL ISCHEMIA/REPERFUSION
    Campolo, M.
    Impellizzeri, D.
    Bruschetta, G.
    Casili, G.
    Esposito, E.
    Cuzzocrea, S.
    SHOCK, 2015, 44 : 9 - 9
  • [44] Diazoxide Decreases Ischemia-Reperfusion Injury in a Rat Model of Lung Transplantation
    Guo, W.
    Ge, D.
    Wang, Q.
    Xu, S.
    Xue, L.
    Lu, C.
    Tan, L.
    TRANSPLANTATION PROCEEDINGS, 2011, 43 (07) : 2510 - 2516
  • [45] HEPARIN DECREASES ISCHEMIA-REPERFUSION INJURY IN ISOLATED CANINE GRACILIS MODEL
    WRIGHT, JG
    KERR, JC
    VALERI, CR
    HOBSON, RW
    ARCHIVES OF SURGERY, 1988, 123 (04) : 470 - 472
  • [46] Investigation of the potential cardioprotective roles of a mitochondria-targeted persulfidation agent, mitosulf, in ischemia reperfusion injury
    Nishimura, T.
    Shih, K. -L.
    Ivanov, I.
    Sauchanka, O.
    Arndt, S.
    Forkink, M.
    Norman, A.
    Hartley, R. C.
    Murphy, M. P.
    Krieg, T.
    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2017, 109 : 55 - 55
  • [47] Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury
    Masuzawa, Akihiro
    Black, Kendra M.
    Pacak, Christina A.
    Ericsson, Maria
    Barnett, Reanne J.
    Drumm, Ciara
    Seth, Pankaj
    Bloch, Donald B.
    Levitsky, Sidney
    Cowan, Douglas B.
    McCully, James D.
    AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2013, 304 (07): : H966 - H982
  • [48] Mitochondria-targeted antioxidant MitoQ reduced renal damage caused by ischemia-reperfusion injury in rodent kidneys: Longitudinal observations of T2-weighted imaging and dynamic contrast-enhanced MRI
    Liu, Xiaoge
    Murphy, Michael P.
    Xing, Wei
    Wu, Huanhuan
    Zhang, Rui
    Sun, Haoran
    MAGNETIC RESONANCE IN MEDICINE, 2018, 79 (03) : 1559 - 1567
  • [49] ACTIVATING ANTI-OXIDANT ENZYMES INHIBIT MYOCARDIAL ISCHEMIA/REPERFUSION INJURY BY NATURAL COMPOUND DERIVATIVE
    Ku, H. C.
    Kuo, Y. H.
    Su, M. J.
    CARDIOLOGY, 2015, 132 : 200 - 200
  • [50] OPTIMIZATION OF MOUSE HEART PERFUSION AS A MODEL OF ISCHEMIA-REPERFUSION INJURY
    SIU, BB
    CHUA, BHL
    FASEB JOURNAL, 1994, 8 (05): : A607 - A607