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Cardioprotective effect of G-CSF administration after coronary reperfusion in swine AMI model

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New Frontiers in Regenerative Medicine

Abstract

[Purpose] Recent studies have suggested that granulocyte colony-stimulating factor (G-CSF) may accelerate angiogenesis or cardio-myogenesis. No previous studies, however, have used large animal models to investigete how clinical doses of G-CSF affect cardiac function after acute myocardial infarction (AMI). [Methods] Diagonal branch of the left anterior descending coronary artery of domestic swine was balloon-occluded for 1-hour and then reperfused. The G-CSF group received a subcutaneous injection of G-CSF at a dose of 5.0/µg/kg/day for 6 days after MI. Left ventriculography was performed 4 weeks after Ml. The number of vessels in the infarcted area were calculated using sections stained by anti-α-smooth muscle actin (SMA) and anti-von Willebrand factor (vWF). Reverse transcription polymerase chain reactions for collagen I, collagen III, and transforming growth factor (TGF)-β were also examined. [Results] The G-CSF group showed a significantly higher ejection fraction and lower end-diastolic volume in left ventriculography. The numbers of α-SMA- and vWF-positive vessels in the G-CSF group were significantly larger. The expression of collagen III mRNA was significantly lower in the G-CSF group in the infarct and border areas. The expression of TGF-β mRNA was significantly lower in the G-CSF group in the border area. [Conclusions] The administration of clinical doses of G-CSF improved cardiac function after reperfusion in AMI. G-CSF confers its effects by accelerating angio-genesis and modifying the wound-healing process.

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References

  1. Laterveer L, Lindley IJ, Hamilton MS, Willemze R, Fibbe WE. Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long term myelolymphoid repopulating ability. Blood 1995;85:2269–75

    PubMed  CAS  Google Scholar 

  2. Lapidot T, Petit I. Current understanding of stem cell mobilization the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 2002;30:973–81

    Article  PubMed  CAS  Google Scholar 

  3. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F et al. Mobi lized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 2001; 98:10344–9

    Article  PubMed  CAS  Google Scholar 

  4. Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, et al. Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 1989;337:471–3

    Article  PubMed  CAS  Google Scholar 

  5. Welte K, Bonilla MA, Gillio AP, Bonne TC, Potter GK, Gabrilove JL, et al. Recombinant human granulocyte colony-stimulating factor effects on hematopoiesis in normal and cyclophosphamide-treated primates. J Exp Med 1987; 165:941–8

    Article  PubMed  CAS  Google Scholar 

  6. Ohtuska M, Takano H, Zou Y, Toko H, Akazawa H, Qin Y, et al. Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization. FASEB J 2004; 18:851–3

    Google Scholar 

  7. Minatoguchi S, Takemura G, Chen XH, Wang N, Uno Y, Koda M, et al. Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment. Circulation 2004; 109:2572–80

    Article  PubMed  CAS  Google Scholar 

  8. Miki T, Miura T, Nishino Y, Yano T, Sakamoto J, Nakamura Y, et al. Granulocyte colony stimulating factor/macrophage colony stimulationg factor improves postinfarct ventricular function by suppression of border zone remodeling in rats. Clin Exp Pharmaco Physiol 2004;31:873–82

    Article  CAS  Google Scholar 

  9. Sugano Y, Anzai T, Yoshikawa T, Maekawa Y, Kohno T, Mahara K, et al. Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction. Cardiovasc Res 2005;65:446–56

    Article  PubMed  CAS  Google Scholar 

  10. Maekawa Y, Anzai T, Yoshikawa T, Sugano Y, Mahara K, Kohno T, et al. Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 2004;44:1510–20

    Article  PubMed  CAS  Google Scholar 

  11. Hill JM, Syed MA, Arai AE, Powell TM, Paul JD, Zalos G, et al. Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease. J Am Coll Cardiol 2005;46:1643–8

    Article  PubMed  CAS  Google Scholar 

  12. Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Koo BK, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilized with granulocyte-colony stimulating factor on left ventricular systolic function and reste-nosis after coronary stenting in myocardial infarction: the MAGIC cell randomized clinical trial. Lancet 2004;363:751–6

    Article  PubMed  CAS  Google Scholar 

  13. Iwanaga K, Takano H, Ohtsuka M, Hasegawa H, Zou Y, Qin Y, et al. Effect of G-CSF on cardiac remodeling after acute myocardial infarction in swine. Biochem Biophys Res Commun 2004;325:1353–9

    Article  PubMed  CAS  Google Scholar 

  14. Hasegawa H, Takano H, Iwanaga K, Ohtsuka M, Qin Y, Niitsuma Y, et al. Cardioprotective effects of granulocyte colony-stimulating factor in swine with chronic myocardial ischemia. J Am Coll Cardiol 2006;47:842–9

    Article  PubMed  CAS  Google Scholar 

  15. Wang JF, Olson ME, Reno CR, Kulyk W, Wright JB, Hart DA. Molecular and cell biology of skin wound healing in a pig model. Connect Tissue Res 2000;41:195–211

    PubMed  CAS  Google Scholar 

  16. Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H, et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nature Med 2005; 11:305–11

    Article  PubMed  CAS  Google Scholar 

  17. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Birkhoff D, Wang J, et al. Neovascularization of ischemic myocardium by human bone marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nature Med 2001;7:430–6

    Article  PubMed  CAS  Google Scholar 

  18. Pfeffer MA, Branwald E. Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation 1990; 81:1161–72

    PubMed  CAS  Google Scholar 

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Sato, T. et al. (2007). Cardioprotective effect of G-CSF administration after coronary reperfusion in swine AMI model. In: Kusano, M., Shioda, S. (eds) New Frontiers in Regenerative Medicine. Springer, Tokyo. https://doi.org/10.1007/978-4-431-38208-9_13

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  • DOI: https://doi.org/10.1007/978-4-431-38208-9_13

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-38207-2

  • Online ISBN: 978-4-431-38208-9

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