Identification of inducible nitric oxide synthase in peripheral blood cells as a mediator of myocardial ischemia/reperfusion injury

被引:22
|
作者
Guo, Yiru [1 ]
Sanganalmath, Santosh K. [1 ]
Wu, Wenjian [1 ]
Zhu, Xiaoping [1 ]
Huang, Yiming [2 ]
Tan, Wei [1 ]
Ildstad, Suzanne T. [2 ]
Li, Qianhong [1 ]
Bolli, Roberto [1 ]
机构
[1] Univ Louisville, Inst Mol Cardiol, Louisville, KY 40202 USA
[2] Univ Louisville, Inst Cellular Therapeut, Louisville, KY 40202 USA
关键词
Inducible nitric oxide synthase; Myocardial infarction; Infarct size; Chimeric mice; SIMULTANEOUS ISLET ALLOGRAFTS; DONOR-SPECIFIC TOLERANCE; K-ATP CHANNELS; CONSCIOUS RABBITS; LATE-PHASE; HEART-FAILURE; GENE-THERAPY; ISCHEMIA-REPERFUSION; POTASSIUM CHANNELS; INFARCTION;
D O I
10.1007/s00395-012-0253-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although the late phase of ischemic preconditioning is known to be mediated by increased inducible nitric oxide synthase (iNOS) activity, controversy persists regarding the role of iNOS in ischemia/reperfusion (I/R) injury and, specifically, whether this protein is protective or detrimental. We hypothesized that iNOS is protective in myocytes but detrimental in inflammatory cells. To test this hypothesis, we created chimeric mice with iNOS-deficient peripheral blood cells by transplanting iNOS knockout (KO) bone marrow in wild-type (WT) mice after lethal irradiation. 2 months later, the mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. In WT naive mice (iNOS(+/+) naive; group I, n = 17), infarct size was 56.9 +/- 2.8% of the risk region. In iNOS KO naive mice with whole-body iNOS deletion (iNOS(-/-) naive; group II, n = 10), infarct size was comparable to group I (53.4 +/- 3.5%). When irradiated WT mice received marrow from WT mice (iNOS(+/+) chimera; group III, n = 10), infarct size was slightly reduced versus group I (44.3 +/- 3.2%), indicating that irradiation and/or transplantation slightly decrease I/R injury. However, when WT mice received marrow from iNOS KO mice (iNOS(-/-) chimera; group IV, n = 14), infarct size was profoundly reduced (22.8 +/- 2.1%, P < 0.05 vs. group III), indicating that selective deletion of iNOS from peripheral blood cells (with no change in myocardial iNOS content) induces protection against myocardial infarction. Together with our previous work showing the cardioprotective actions of NO donors, iNOS gene therapy, and cardiac-specific overexpression of iNOS, these data support a complex, dual role of iNOS in myocardial infarction (i.e., protective in myocytes but deleterious in blood cells). To our knowledge, this is the first study to identify a critical role of iNOS in peripheral blood cells as a mediator of myocardial I/R injury. The results support heretofore unknown differential actions of iNOS depending on cell source and have important translational implications.
引用
收藏
页数:8
相关论文
共 50 条
  • [1] Identification of Inducible Nitric Oxide Synthase in Peripheral Blood Cells as a Mediator of Myocardial Ischemia/Reperfusion Injury
    Guo, Yiru
    Huang, Yiming
    Wu, Wen-Jian
    Zhu, Xiaoping
    Dawn, Buddhadeb
    Tan, Wei
    Rokosh, Gregg
    Ildstad, Suzanne T.
    Bolli, Roberto
    [J]. CIRCULATION, 2008, 118 (18) : S292 - S292
  • [2] Identification of inducible nitric oxide synthase in peripheral blood cells as a mediator of myocardial ischemia/reperfusion injury
    Yiru Guo
    Santosh K. Sanganalmath
    Wenjian Wu
    Xiaoping Zhu
    Yiming Huang
    Wei Tan
    Suzanne T. Ildstad
    Qianhong Li
    Roberto Bolli
    [J]. Basic Research in Cardiology, 2012, 107
  • [3] Attenuation of myocardial ischemia/reperfusion injury by superinduction of inducible nitric oxide synthase
    Kanno, S
    Lee, PC
    Zhang, YQ
    Ho, C
    Griffith, BP
    Shears, LL
    Billiar, TR
    [J]. CIRCULATION, 2000, 101 (23) : 2742 - 2748
  • [4] Myocardial ischemia/reperfusion injury in the inducible nitric oxide synthase knockout mice
    Xi, L
    Jarrett, NC
    Hess, ML
    Kukreja, RC
    [J]. LIFE SCIENCES, 1999, 65 (09) : 935 - 945
  • [5] The Dual Role of Inducible Nitric Oxide Synthase in Myocardial Ischemia/Reperfusion Injury: Friend or Foe?
    Yu, Xin
    Ge, Liang
    Niu, Liang
    Lian, Xin
    Ma, Haichun
    Pang, Lei
    [J]. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2018, 2018
  • [6] Inducible nitric oxide synthase in retinal ischemia-reperfusion injury
    Hangai, M
    Yoshimura, N
    Hiroi, K
    Mandai, M
    Honda, Y
    [J]. EXPERIMENTAL EYE RESEARCH, 1996, 63 (05) : 501 - 509
  • [7] Role of inducible nitric oxide synthase on hepatic ischemia and reperfusion injury
    Isobe, M
    Katsuramaki, T
    Kimura, H
    Nagayama, M
    Matsuno, T
    Yagihashi, A
    Hirata, K
    [J]. TRANSPLANTATION PROCEEDINGS, 2000, 32 (07) : 1650 - 1652
  • [8] Inducible nitric oxide synthase in retinal ischemia-reperfusion injury
    Kuroiwa, S
    Shibuki, H
    Yoshimura, N
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 1999, 40 (04) : S483 - S483
  • [9] Inhibition of Inducible Nitric Oxide Synthase Ameliorates Myocardial Ischemia/Reperfusion Injury - Induced Acute Renal Injury
    Chen, T. -H.
    Liao, F. -T.
    Yang, Y. -C.
    Wang, J. -J.
    [J]. TRANSPLANTATION PROCEEDINGS, 2014, 46 (04) : 1123 - 1126
  • [10] Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury
    Chatterjee, PK
    Patel, NSA
    Kvale, EO
    Cuzzocrea, S
    Brown, PAJ
    Stewart, KN
    Mota-Filipe, H
    Thiemermann, C
    [J]. KIDNEY INTERNATIONAL, 2002, 61 (03) : 862 - 871