Identification of a novel role of T cells in postnatal vasculogenesis - Characterization of endothelial progenitor cell colonies
Identification of a novel role of T cells in postnatal vasculogenesis - Characterization of endothelial progenitor cell colonies
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DOI：
10.1161/circulationaha.107.694778
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发表时间：
2007-10-09
期刊：
影响因子：
37.8
通讯作者：
Kim, Hyo-Soo
中科院分区：
文献类型：
--
作者：
Hur, Jin;Yang, Han-Mo;Kim, Hyo-Soo
背景-早期内皮祖细胞的集落数量已被用作血液中内皮祖细胞数量的定量指标或作为心血管疾病的生物标志。方法和结果：在人外周血单个核细胞培养过程中，发现CD3(+)CD31(+)CXCR4(+)T细胞(在本研究中称为血管生成T细胞)构成了EPC克隆的中心。这些血管生成T细胞是早期内皮祖细胞集落形成和分化所必需的。它们分泌高水平的血管生成细胞因子，如血管内皮生长因子、白细胞介素8和基质金属蛋白酶。血管生成T细胞主要通过基质细胞衍生因子1/CXCR-4轴，在Matrigel管的形成、黏附、跨内皮细胞迁移和胶原侵袭实验中显示出优于其他T细胞亚群的血管生成潜力。此外，血管生成T细胞促进内皮细胞的增殖和功能。体内研究表明，血管生成T细胞在血管形成过程中起着重要作用。临床研究表明，外周血中血管生成T细胞水平与EPC集落数呈正相关，与年龄、冠心病危险因素数呈负相关。结论：血管生成T细胞可能成为治疗缺血性心血管疾病的潜在靶点。
Background - The colony number of early endothelial progenitor cells ( EPCs) has been used as a quantitative indicator of the number of EPCs in the blood or as a biological marker of cardiovascular diseases. In the present study, we found a subset of T cells that were localized at the center of the EPC colony and played a pivotal role in colony formation and differentiation of early EPCs.Methods and Results - We found that CD3(+)CD31(+)CXCR4(+) T cells ( referred to as angiogenic T cells in the present study) constituted the center of EPC colonies during cultures of human peripheral blood mononuclear cells. These angiogenic T cells were required for colony formation and differentiation of early EPCs. They secreted high levels of angiogenic cytokines such as vascular endothelial growth factor, interleukin- 8, and matrix metalloproteinases. Angiogenic T cells showed superior angiogenic potential to the other subset of T cells in the experiments with regard to Matrigel tube formation, adhesion, transendothelial migration, and collagen invasion assay, mainly through the stromal cell - derived factor 1/CXCR- 4 axis. Furthermore, angiogenic T cells enhanced endothelial cell proliferation and function. In vivo study showed that angiogenic T cells play an important role in the process of vessel formation. Clinical study showed that the level of angiogenic T cells in the peripheral blood was well correlated with EPC colony numbers and had inverse relationships with age and the number of risk factors for coronary artery disease.Conclusions - These findings suggest that angiogenic T cells could be a potential therapeutic target for ischemic cardiovascular diseases.