Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function
Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function
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DOI：
10.1038/86498
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发表时间：
2001-04-01
期刊：
影响因子：
82.9
通讯作者：
Itescu, S
中科院分区：
文献类型：
--
作者：
Kocher, AA;Schuster, MD;Itescu, S
左心室重构是心梗后进行性心力衰竭和死亡的主要原因。尽管梗死组织内的新血管生成是重构过程的一个组成部分，但毛细血管网络无法支持肥厚心肌的更大需求，导致活组织的逐渐丧失、梗死延伸和纤维替代。本研究表明，成人骨髓中含有具有胚胎成血管细胞表型和功能特征的内皮前体细胞，这些内皮前体细胞可用于直接诱导梗死床中新血管的形成（血管生成）和实验性心肌梗死后原有血管的增殖（血管生成）。新血管生成导致梗死周围肥大肌细胞凋亡减少，存活心肌的长期挽救和存活，胶原沉积减少，心功能持续改善。使用细胞因子动员的自体人骨髓源性成血管细胞用于梗死心肌的血运重建（单独或与目前使用的疗法联合使用）有可能显著降低与左心室重构相关的发病率和死亡率。
Left ventricular remodeling is a major cause of progressive heart failure and death after myocardial infarction. Although neoangiogenesis within the infarcted tissue is an integral component of the remodeling process, the capillary network is unable to support the greater demands of the hypertrophied myocardium, resulting in progressive loss of viable tissue, infarct extension and fibrous replacement. Here we show that bone marrow from adult humans contains endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to directly induce new blood vessel formation in the infarct-bed (vasculogenesis) and proliferation of preexisting vasculature (angiogenesis) after experimental myocardial infarction. The neoangiogenesis resulted in decreased apoptosis of hypertrophied myocytes in the peri-infarct region, long-term salvage and survival of viable myocardium, reduction in collagen deposition and sustained improvement in cardiac function. The use of cytokine-mobilized autologous human bone-marrow-derived angioblasts for revascularization of infarcted myocardium (alone or in conjunction with currently used therapies) has the potential to significantly reduce morbidity and mortality associated with left ventricular remodeling.