Ischemic Pre-Conditioning Enhances the Mobilization and Recruitment of Bone Marrow Stem Cells to Protect Against Ischemia/Reperfusion Injury in the Late Phase
Ischemic Pre-Conditioning Enhances the Mobilization and Recruitment of Bone Marrow Stem Cells to Protect Against Ischemia/Reperfusion Injury in the Late Phase
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DOI：
10.1016/j.jacc.2009.02.015
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发表时间：
2009-05-12
影响因子：
24
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Kamota, Takahiro;Li, Tao-Sheng;Hamano, Kimikazu
目的探讨骨髓干细胞(BMSCs)在缺血预适应(IPC)后后期的动员和募集是否有助于心肌保护。背景：IPC是一种先天现象，短暂暴露于亚致死性缺血可保护组织免受随后的缺血/再灌注(I/R)损伤。IPC后也出现延迟的心脏保护，但确切的机制尚不清楚。方法采用小鼠腹主动脉阻断和再灌流5分钟的4个循环建立IPC模型。结果缺血后1h和3h血清血管内皮生长因子和基质细胞衍生因子-1α水平显著升高，而外周血中CD34+和CD34+/Flk-1+干细胞水平显著升高(p<；0.05)。与对照组相比，IPC早期和晚期对心肌I/R损伤均有保护作用。然而，在缺血再灌注损伤晚期，骨髓间充质干细胞在心脏的募集明显多于缺血预适应早期(p<；0.01)。有趣的是，阻断BMSCs的募集明显减弱了IPC的心肌保护作用(P<；0.01)，但在早期并没有改变。结论在IPC的早期和晚期都观察到了心肌保护作用，但BMSCs的动员和募集在IPC的晚期起着重要的作用。(J Am Coll心脏ol 2009；53：1814-22)(C)美国心脏病学会基金会2009年
Objectives The aim of this study was to investigate whether the mobilization and recruitment of bone marrow stem cells (BMSCs) contribute to cardioprotection in the late phase after ischemic pre-conditioning (IPC).Background IPC is an innate phenomenon in which brief exposure to sublethal ischemia provides tissue protection from subsequent ischemia/reperfusion (I/R) injury. A delayed cardioprotection also occurs after IPC, but the precise mechanism is unclear.Methods IPC was created with 4 cycles of 5-min occlusion and reperfusion of the abdominal aorta in mice. Heart I/R injury was induced by occluding the left anterior descending artery for 30 min immediately (early phase) or 24 h (late phase) after IPC.Results Serum vascular endothelial growth factor and stromal cell-derived factor-1 alpha levels were increased significantly 1 and 3 h after IPC, but CD34+ and CD34+/flk-1+ stem cells in the peripheral blood were increased significantly 12 and 24 h after IPC (p < 0.05). Compared with the control treatment, both the early and late phases of IPC protected the heart against I/R injury. However, the recruitment of BMSCs was significantly greater in the heart when I/R injury was induced in late phase than in the early phase of IPC (p < 0.01). Interestingly, the blockade of the recruitment of BMSCs significantly attenuated the cardioprotective effect of IPC in the late phase (p < 0.01) but did not change in the early phase.Conclusions Cardioprotection was observed in the early and late phases of IPC; however, the enhanced mobilization and recruitment of BMSCs played an important role in the late phase of IPC. (J Am Coll Cardiol 2009; 53: 1814-22) (C) 2009 by the American College of Cardiology Foundation