Université Paris Descartes, Paris, France.
Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):551-9. doi: 10.1161/ATVBAHA.110.220624. Epub 2010 Dec 9.
We examined whether plasma levels of angiogenic factors are altered in plasma of patients with peripheral arterial disease (PAD) and whether these factors affect endothelial progenitor cell-induced angiogenesis.
Plasma was collected from 184 patients with PAD and 330 age-matched healthy controls. Vascular endothelial growth factor and placental growth factor concentrations did not differ between the groups, whereas we found a linear correlation between PAD disease and thrombospondin (TSP)-1 plasma level. TSP-1 was expressed in newly formed vessels in PAD patients having received local injections of bone marrow mononuclear cells. To analyze the functional role of TSP-1 during neoangiogenesis, we used a Matrigel-plug assay and showed that vascularization of implanted Matrigel-plugs was increased in TSP-1(-/-) mice. Moreover, injections of TSP-1 in C57Bl6/J mice after hindlimb ischemia induced a significant decrease of blood flow recovery. To investigate the effects of TSP-1 on human endothelial colony-forming cell (ECFC) angiogenic potential, recombinant human TSP-1 and a small interfering RNA were used. In vitro, TSP-1 N-terminal part significantly enhanced ECFC adhesion, whereas recombinant human TSP-1 had a negative effect on ECFC angiogenic potential. This effect, mediated by CD47 binding, modulated stromal cell-derived factor 1/CXC chemokine receptor 4 pathway.
TSP-1 is a potential biomarker of PAD and ECFC-induced angiogenesis, suggesting that TSP-1 modulation might improve local tissue ischemia in this setting. (
NCT00377897.).
我们研究了外周动脉疾病（PAD）患者的血浆中血管生成因子的水平是否发生改变，以及这些因子是否影响内皮祖细胞诱导的血管生成。
从 184 名 PAD 患者和 330 名年龄匹配的健康对照者中采集了血浆。血管内皮生长因子和胎盘生长因子的浓度在两组之间没有差异，而我们发现 PAD 疾病与血小板反应蛋白-1（TSP-1）的血浆水平之间存在线性相关性。TSP-1 在接受骨髓单核细胞局部注射的 PAD 患者的新形成血管中表达。为了分析 TSP-1 在新血管生成过程中的功能作用，我们使用了 Matrigel 塞栓分析，并表明在 TSP-1（-/-）小鼠中植入的 Matrigel 塞栓的血管化增加。此外，在小鼠后肢缺血后注射 TSP-1 可导致血流恢复显著减少。为了研究 TSP-1 对人内皮集落形成细胞（ECFC）血管生成潜能的影响，我们使用了重组人 TSP-1 和小干扰 RNA。在体外，TSP-1 N 端部分显著增强了 ECFC 的黏附能力，而重组人 TSP-1 对 ECFC 的血管生成潜能有负作用。这种效应通过与 CD47 结合而介导，调节基质细胞衍生因子 1/CXC 趋化因子受体 4 途径。
TSP-1 是 PAD 的潜在生物标志物，也是 ECFC 诱导的血管生成的标志物，表明 TSP-1 调节可能改善这种情况下的局部组织缺血。（临床试验注册号：NCT00377897）。
