Cathepsin L is required for endothelial progenitor cell-induced neovascularization
Cathepsin L is required for endothelial progenitor cell-induced neovascularization
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DOI：
10.1038/nm1182
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发表时间：
2005-02-01
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：
Urbich, C;Heeschen, C;Dimmeler, S
输注内皮祖细胞（EPC），但不输注成熟内皮细胞，可促进缺血后的新血管形成。我们对 EPC 和内皮细胞进行了基因表达谱分析，以确定可能对 EPC 的新生血管形成能力重要的基因。值得注意的是，与内皮细胞相比，蛋白酶组织蛋白酶 L (CathL) 在 EPC 中高表达，并且对于 EPC 体外基质降解和侵袭至关重要。 CathL 缺陷小鼠在后肢缺血后表现出功能恢复受损，这支持了 CathL 在出生后新生血管形成中发挥关键作用的概念。输注的 CathL 缺陷祖细胞既不归巢于缺血部位，也不增强新血管形成。 CathL在成熟内皮细胞中的强制表达显着增强了它们的侵袭活性并足以赋予它们体内新血管形成的能力。我们得出的结论是，CathL 在循环 EPC 整合到缺血组织中具有关键作用，并且是 EPC 介导的新血管形成所必需的。
Infusion of endothelial progenitor cells (EPC), but not of mature endothelial cells, promotes neovascularization after ischemia. We performed gene expression profiling of EPC and endothelial cells to identify genes that might be important for the neovascularization capacity of EPC. Notably, the protease cathepsin L (CathL) was highly expressed in EPC as opposed to endothelial cells and was essential for matrix degradation and invasion by EPC in vitro. CathL-deficient mice showed impaired functional recovery following hind limb ischemia, supporting the concept of a crucial role for CathL in postnatal neovascularization. Infused CathL-deficient progenitor cells neither homed to sites of ischemia nor augmented neovascularization. Forced expression of CathL in mature endothelial cells considerably enhanced their invasive activity and sufficed to confer their capacity for neovascularization in vivo. We concluded that CathL has a critical role in the integration of circulating EPC into ischemic tissue and is required for EPC-mediated neovascularization.