Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization
Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization
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DOI：
10.1182/blood-2003-01-0223
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发表时间：
2003-08-15
期刊：
影响因子：
20.3
通讯作者：
Dimmeler, S
中科院分区：
文献类型：
--
作者：
Heeschen, C;Aicher, A;Dimmeler, S
越来越多的证据表明，出生后新生血管涉及循环内皮祖细胞(EPC)的募集。造血系和内皮细胞系拥有共同的祖细胞。以前被认为是造血系统特有的细胞因子，直到最近才被证明影响内皮细胞的几种功能。因此，我们研究了促红细胞生成素(EPO)对EPC动员和新生血管的刺激作用。EPO处理的小鼠骨髓中干细胞和祖细胞以及集落形成单位的数量和增殖显著增加。EPO处理组小鼠脾和外周血中分离的EPC和CD34(+)/Flk-1(+)前体细胞数明显高于磷酸盐缓冲液生理盐水处理组小鼠。在出生后新生血管的活体模型中，EPO显著增加炎症和缺血诱导的新生血管。在冠心病患者中，研究了这些发现的生理学相关性。在多元回归模型中，血清EPO和血管内皮生长因子水平与骨髓中干细胞和祖细胞的数量以及循环内皮祖细胞的数量和功能显著相关。综上所述，本研究提示EPO至少部分通过促进骨髓内皮祖细胞动员来刺激出生后新生血管形成。EPO似乎在生理上调节了缺血性心脏病患者的EPC动员。因此，EPO血清水平可能有助于识别EPC募集能力受损的患者。(C)2003年，由美国血液病学会提供。
Increasing evidence suggests that postnatal neovascularization involves the recruitment of circulating endothelial progenitor cells (EPCs). Hematopoietic and endothelial cell lineages share common progenitors. Cytokines formerly thought to be specific for the hematopoietic system have only recently been shown to affect several functions in endothelial cells. Accordingly, we investigated the stimulatory potential of erythropoietin (Epo) on EPC mobilization and neovascularization. The bone marrow of Epo-treated mice showed a significant increase in number and proliferation of stem and progenitor cells as well as in colony-forming units. The number of isolated EPCs and CD34(+)/flk-1(+) precursor cells was significantly increased in spleen and peripheral blood of Epo-treated mice compared with phosphate-buffered saline-treated mice. In in vivo models of postnatal neovascularization, Epo significantly increased inflammation- and ischemia-induced neovascularization. The physiologic relevance of these findings was investigated in patients with coronary heart disease. In a multivariate regression model, serum levels of Epo and vascular endothelial growth factor were significantly associated with the number of stem and progenitor cells in the bone marrow as well as with the number and function of circulating EPCs. In conclusion, the present study suggests that Epo stimulates postnatal neovascularization at least in part by enhancing EPC mobilization from the bone marrow. Epo appears to physiologically regulate EPC mobilization in patients with ischemic heart disease. Thus, Epo serum levels may help in identifying patients with impaired EPC recruitment capacity. (C) 2003 by The American Society of Hematology.