Smadja D M, Laurendeau I, Avignon C, Vidaud M, Aiach M, Gaussem P
Université Paris-Descartes, INSERM Unité 765, Hôpital Européen Georges Pompidou, Paris, France.
J Thromb Haemost. 2006 Sep;4(9):2051-8. doi: 10.1111/j.1538-7836.2006.02101.x. Epub 2006 Jun 27.
The importance of protease-activated receptor-1 (PAR-1) in blood vessel development has been shown in knock-out mice. As endothelial progenitor cells (EPCs) express functional PAR-1, we examined whether PAR-1 stimulation by the peptide SFLLRN interfered with the angiopoietin pathway, that is EPC commitment, proliferation and migration.
Given the strong PAR-1 expression on CD34+ cells, we tested the effect of SFLLRN 75 micromol L(-1) on the emergence of EPCs from cord blood. PAR-1 activation did not modify the number of colonies or the day of emergence, in keeping with the lack of induction of angiopoietin 1 gene expression. Conversely, SFLLRN treatment of EPCs induced angiopoietin 2 gene expression and protein synthesis. Experiments with polyclonal blocking antibodies showed that angiopoietin 2 was involved in the proliferative effect of PAR-1 activation. PAR-1 activation also enhanced migration toward angiopoietin 1 in a Boyden chamber assay.
Our study demonstrates that PAR-1-induced proliferation of EPCs involves angiopoietin 2. PAR-1 also enhances EPC migration toward angiopoietin 1. These findings might explain the role of thrombin in neovascularization via the angiopoietin pathway.
蛋白酶激活受体-1（PAR-1）在血管发育中的重要性已在基因敲除小鼠中得到证实。由于内皮祖细胞（EPCs）表达功能性PAR-1，我们研究了肽SFLLRN对PAR-1的刺激是否会干扰血管生成素途径，即EPC的定向分化、增殖和迁移。
鉴于CD34+细胞上PAR-1的强表达，我们测试了75微摩尔/升的SFLLRN对脐血中EPCs出现的影响。PAR-1激活并未改变集落数量或出现的天数，这与血管生成素1基因表达未被诱导一致。相反，用SFLLRN处理EPCs可诱导血管生成素2基因表达和蛋白质合成。使用多克隆阻断抗体的实验表明，血管生成素2参与了PAR-1激活的增殖效应。在Boyden小室试验中，PAR-1激活还增强了EPCs向血管生成素1的迁移。
我们的研究表明，PAR-1诱导的EPCs增殖涉及血管生成素2。PAR-1还增强了EPCs向血管生成素1的迁移。这些发现可能解释了凝血酶通过血管生成素途径在新生血管形成中的作用。
