Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-GSF
Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-GSF
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DOI：
10.1016/j.cardiores.2006.05.002
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发表时间：
2006-08-01
影响因子：
10.8
通讯作者：
Fujiwara, Hisayoshi
中科院分区：
文献类型：
--
作者：
Misao, Yu;Takemura, Genzou;Fujiwara, Hisayoshi
目的：粒细胞集落刺激因子（G-CSF）促进心肌梗死（MI）后的修复。最近，据报道，心肌梗死后给予G-CSF的有益作用是通过直接激活心肌细胞中的Jak-Stat通路介导的。我们的目的是测试的假设，骨髓来源的细胞招募到梗死心肌的有益效果的主要介质由G-CSF.Methods和结果：MI诱导使用30分钟的缺血再灌注协议（0天）在40只兔用G-CSF（10微克/公斤/天，从第3天至第7天）或盐水。另外40只兔子接受相同的G-CSF或盐水方案，但也接受AMD 3100（200 μ g/kg/天），一种CXCR 4的特异性抑制剂。在MI后第28天，G-CSF组的左心室射血分数和舒张末期尺寸显著优于对照盐水组，G-CSF组的瘢痕面积/左心室壁面积比显著较小。G-CSF给药还导致CXCR 4（+）骨髓细胞动员增加，包括。RAM 11+巨噬细胞，进入梗死区域。在这些区域内，基质细胞衍生因子（SDF）-1（循环CXCR 4+细胞的化学引诱物）以及胶原酶基质金属蛋白酶-1的表达显著上调。AMD 3100可显著抑制G-CSF的上述作用，但不影响SDF-1和磷酸化Stat 3的表达。结论：通过刺激CXCR 4/SDF-1轴募集CXCR 4+细胞进入梗死心肌组织在G-CSF的作用中起重要作用。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Granulocyte-colony stimulating factor (G-CSF) accelerates repair following myocardial infarction (MI). Recently, the beneficial effects of post-MI administration of G-CSF were reported to be mediated by direct activation of the Jak-Stat pathway in cardiomyocytes. Our aim was to test the hypothesis that bone marrow-derived cells recruited into the infarcted myocardium are the primary mediators of the beneficial effects by G-CSF.Methods and results: MI was induced using a 30-min ischemia-reperfusion protocol (day 0) in 40 rabbits treated with G-CSF (10 mu g/kg/day from days 3 to 7) or saline. Another 40 rabbits received the same G-CSF or saline protocol but also received AMD3100 (200 mu g/kg/day), a specific inhibitor of CXCR4. On day 28 post-MI, left ventricular ejection fractions and end-diastolic dimensions were significantly better in the G-CSF group than in the control saline group, and the scar area/left ventricular wall area ratio was significantly smaller in the G-CSF group. G-CSF administration also led to increased mobilization of CXCR4(+) bone marrow cells, including. RAM11+ macrophages, into infarcted areas. And within those areas there was significant upregulation of expression of stromal cell-derived factor (SDF)-1, a chemoattractant of circulating CXCR4+ cells, as well as of the collagenase matrix metalloprotemase-1. AMD3100 significantly inhibited all of these beneficial effects of G-CSF, but did not affect the upregulation of SDF-1 or phospho-Stat3.Conclusion: Recruitment of CXCR4+ cells into infarcted myocardial tissues via stimulation of the CXCR4/SDF-1 axis plays a critical role in the beneficial effects of G-CSF. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.