Migration of bone marrow-derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction.
Migration of bone marrow-derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction.
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DOI：
10.1111/j.1582-4934.2011.01286.x
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发表时间：
2012-01
影响因子：
5.3
通讯作者：
Franz WM
中科院分区：
文献类型：
--
作者：
Brunner S;Huber BC;Weinberger T;Vallaster M;Wollenweber T;Gerbitz A;Hacker M;Franz WM
促红细胞生成素（EPO）通过血管生成和抗凋亡机制对心肌梗死（MI）后有保护作用。除了直接的受体依赖性机制外，骨髓源性细胞（BMC）的动员和归巢可能在这方面发挥关键作用。在这项研究中，我们打算跟踪不同亚群的BMC，并连续评估心肌缺血后EPO治疗的小鼠心肌灌注的变化。为了允许跟踪BMC，我们使用嵌合小鼠模型。因此，对小鼠（C57 BL/6 J）进行亚致死剂量照射，并移植来自绿色荧光蛋白转基因小鼠的骨髓（BM）。10周后进行冠状动脉结扎以诱导MI。EPO注射3天，总剂量为5000 IU/kg。通过流式细胞术研究了外周血、骨髓和心脏中EGFP+细胞的亚群（CD 31、c-kit、CXCR-4和Sca-1）。在MI后第6天和第30天，通过针孔单光子发射计算机断层扫描（SPECT）连续研究心肌灌注。EPO处理的动物显示出增强的动员BMC进入外周血。BM中这些细胞的数量保持不变。EPO处理的小鼠中，所有BMC亚群向缺血心肌的归巢显著增加。在研究的亚群中，EPO主要影响CXCR-4+的迁移（增加4.3倍）。重复SPECT分析显示EPO治疗后灌注缺陷随时间减少。我们的研究表明，促红细胞生成素治疗后，心肌梗死增强骨髓细胞迁移到缺血组织的能力，这可能是由于改善灌注和缩小梗死面积，分别。
Erythropoietin (EPO) was shown to have protective effects after myocardial infarction (MI) by neovascularization and antiapoptotic mechanisms. Beside direct receptor-dependent mechanisms, mobilization and homing of bone marrow-derived cells (BMCs) may play a pivotal role in this regard. In this study, we intended to track different subpopulations of BMCs and to assess serially myocardial perfusion changes in EPO-treated mice after MI. To allow tracking of BMCs, we used a chimeric mouse model. Therefore, mice (C57BL/6J) were sublethally irradiated, and bone marrow (BM) from green fluorescent protein transgenic mice was transplanted. Ten weeks later coronary artery ligation was performed to induce MI. EPO was injected for 3 days with a total dose of 5000 IU/kg. Subpopulations (CD31, c-kit, CXCR-4 and Sca-1) of EGFP+ cells were studied in peripheral blood, bone marrow and hearts by flow cytometry. Myocardial perfusion was serially investigated in vivo by pinhole single-photon emission computed tomography (SPECT) at days 6 and 30 after MI. EPO-treated animals revealed an enhanced mobilization of BMCs into peripheral blood. The numbers of these cells in BM remained unchanged. Homing of all BMCs subpopulations to the ischaemic myocardium was significantly increased in EPO-treated mice. Among the investigated subpopulations, EPO predominantly affected migration of CXCR-4+ (4.3-fold increase). Repetitively SPECT analyses revealed a reduction of perfusion defects after EPO treatment over time. Our study shows that EPO treatment after MI enhances the migration capacity of BMCs into ischaemic tissue, which may attribute to an improved perfusion and reduced size of infarction, respectively.
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影响因子：
20.3
作者：
Freedman, A;Neuberg, D;Nadler, L
通讯作者：
Nadler, L
影响因子：
20.3
作者：
van Os, R;Robinson, S;Mauch, PM
通讯作者：
Mauch, PM
影响因子：
82.9
作者：
Kocher, AA;Schuster, MD;Itescu, S
通讯作者：
Itescu, S
影响因子：
37.8
作者：
Cai, ZQ;Semenza, GL
通讯作者：
Semenza, GL
影响因子：
39.3
作者：
Voors, Adriaan A.;Belonje, Anne M. S.;van Veldhuisen, Dirk J.
通讯作者：
van Veldhuisen, Dirk J.