The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment
The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment
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DOI：
10.1016/j.jtcvs.2006.12.026
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发表时间：
2007-04-01
影响因子：
6
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Suzuki, Ryo;Li, Tao-Sheng;Hamano, Kimikazu
目的：有丝分裂的心肌细胞和心脏干细胞最近已被确定在成人心脏，并已被发现在急性心肌梗死增加。虽然这些发现提示了损伤后心脏的潜在自我修复，但临床上从未观察到明显的损伤心脏的自我再生。方法：结扎C57 BL/6小鼠左前降支建立心肌梗死模型。60分钟后，将梗死心脏异位移植到健康受体C57 BL/6小鼠中以去除心室血流动力学负荷（卸载组），或者将其作为正常血流动力学负荷条件下的梗死心脏留在同一小鼠中（负荷组）。结果：与负荷组相比，去负荷组心肌梗死面积明显减小，心肌梗死后3、7、14、28 d心肌梗死面积明显减小，心肌梗死后3、7、14、28 d心肌梗死面积明显减小，心肌梗死后3、14、28 d心肌梗死面积明显减小。免疫组化分析显示，卸载组梗死心肌中Ki-67阳性细胞明显多于负载组，凋亡细胞明显少于负载组。也有显着更多的c-kit-和Sca-1-阳性干细胞在梗死心肌中的卸载组比在loadinggroup.Conclusion：我们的研究结果表明，血流动力学卸载有助于自我再生的损伤心脏通过增加细胞增殖，抑制细胞凋亡，并诱导干细胞募集。
Objectives: Mitotic cardiomyocytes and cardiac stem cells have been identified recently in adult hearts, and both have been found to be increased in acute infarcted myocardium. Although these findings suggest potential self-repair of the heart after injury, obvious self-regeneration of the injured heart has never been observed clinically. We hypothesized that hemodynamic loading impairs myocardial repair.Methods: Myocardial infarction was induced in C57BL/6 mice by ligating the left anterior descending artery. After 60 minutes, either the infarcted heart was transplanted heterotopically into a healthy recipient C57BL/6 mouse to remove the ventricular hemodynamic loading ( unloading group) or it was left as an infarcted heart under normal hemodynamic loading conditions in the same mouse ( loading group). The infarcted hearts were dissected for histologic analysis after 3, 7, 14, and 28 days.Results: Histologic analysis showed that the wall thickness of the infarcted left ventricle was significantly greater and the area of infarction was significantly smaller in the unloading group than in the loading group. Immunostaining analysis revealed significantly more Ki-67-positive cells and significantly fewer apoptotic cells in the infarcted myocardium in the unloading group than in the loading group. There were also significantly more c-kit- and Sca-1-positive stem cells in the infarcted myocardium in the unloading group than in the loading group.Conclusion: Our findings suggest that hemodynamic unloading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment.