Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells
Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells
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DOI：
10.1038/nm948
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发表时间：
2003-11-01
期刊：
影响因子：
82.9
通讯作者：
Dimmeler, S
中科院分区：
文献类型：
--
作者：
Aicher, A;Heeschen, C;Dimmeler, S
内皮型一氧化氮合酶（eNOS）对新生血管的形成至关重要。本研究表明，缺乏eNOS的小鼠新生血管受损与祖细胞动员缺陷有关。缺乏eNOS （Nos3(-/-)）的小鼠显示血管内皮生长因子（VEGF）诱导的内皮祖细胞（EPCs）动员减少，骨髓抑制后死亡率增加。在后肢缺血模型中，静脉输注野生型祖细胞，而不是骨髓移植，可以挽救Nos3（-/-）小鼠新生血管的缺陷，这表明Nos3（-/-）小鼠骨髓祖细胞的动员功能受损。在机制上，干细胞动员所需的基质金属蛋白酶-9 （MMP-9）在Nos3（-/-）小鼠骨髓中减少。这些结果表明，骨髓基质细胞表达的eNOS影响干细胞和祖细胞的募集。这可能有助于缺血性心脏病患者的再生过程受损，其特征是全身NO生物活性降低。
Endothelial nitric oxide synthase (eNOS) is essential for neovascularization. Here we show that the impaired neovascularization in mice lacking eNOS is related to a defect in progenitor cell mobilization. Mice deficient in eNOS (Nos3(-/-)) show reduced vascular endothelial growth factor (VEGF)-induced mobilization of endothelial progenitor cells (EPCs) and increased mortality after myelosuppression. Intravenous infusion of wild-type progenitor cells, but not bone marrow transplantation, rescued the defective neovascularization of Nos3(-/-) mice in a model of hind-limb ischemia, suggesting that progenitor mobilization from the bone marrow is impaired in Nos3(-/-) mice. Mechanistically, matrix metalloproteinase-9 (MMP-9), which is required for stem cell mobilization, was reduced in the bone marrow of Nos3(-/-) mice. These findings indicate that eNOS expressed by bone marrow stromal cells influences recruitment of stem and progenitor cells. This may contribute to impaired regeneration processes in ischemic heart disease patients, who are characterized by a reduced systemic NO bioactivity.