Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration
Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration
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DOI：
10.1152/ajpheart.00058.2004
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发表时间：
2004-08-01
影响因子：
4.8
通讯作者：
Itescu, S
中科院分区：
文献类型：
--
作者：
Schuster, MD;Kocher, AA;Itescu, S
心脏对缺血性损伤的主要反应是心肌细胞肥大，这启动了一种遗传程序，最终导致心肌细胞凋亡性丢失，进行性胶原替代。和心力衰竭，这一过程称为心脏重塑。虽然梗塞周围的少数心肌细胞可以在损伤后增殖和再生，但目前还没有有效地诱导内源性心肌细胞进入细胞周期的方法。我们最近在成人骨髓中分离出内皮祖细胞或血管母细胞，它们迁移到缺血心肌，在那里它们诱导新生血管并防止心肌重塑。在这里，我们显示，增加血管母细胞向梗死区转移的数量会导致剂量依赖性的新生血管形成，并逐渐形成更大的毛细血管。这导致心脏功能的持续改善，其机制包括防止细胞凋亡和诱导内源性心肌细胞的增殖/再生。我们的结果提示，增加骨髓成血管细胞心肌归巢的药物可以有效地诱导内源性心肌细胞进入细胞周期，促进心脏功能恢复。
The primary cardiac response to ischemic insult is cardiomyocyte hypertrophy, which initiates a genetic program culminating in apoptotic myocyte loss, progressive collagen replacement. and heart failure, a process termed cardiac remodeling. Although a few cardiomyocytes at the peri-infarct region can proliferate and regenerate after injury, no approaches are known to effectively induce endogenous cardiomyocytes to enter the cell cycle. We recently isolated, in human adult bone marrow, endothelial progenitor cells, or angioblasts, that migrate to ischemic myocardium, where they induce neovascularization and prevent myocardial remodeling. Here we show that increasing the number of angioblasts trafficking to the infarct zone results in dose-dependent neovascularization with development of progressively larger-sized capillaries. This results in sustained improvement in cardiac function by mechanisms involving protection against apoptosis and, strikingly, induction of proliferation/regeneration of endogenous cardiomyocytes. Our results suggest that agents that increase myocardial homing of bone marrow angioblasts could effectively induce endogenous Cardiomyocytes to enter the cell cycle and improve functional cardiac recovery.