Rafat Neysan, Beck Grietje Ch, Peña-Tapia Pablo G, Schmiedek Peter, Vajkoczy Peter
Department of Anaesthesiology, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Stroke. 2009 Feb;40(2):432-8. doi: 10.1161/STROKEAHA.108.529420. Epub 2008 Dec 18.
Chronic cerebral ischemia leads to higher risk for strokes attributable to insufficient collateralization, resulting from inadequate capacity for arteriogenesis and angiogenesis. Patients with Moyamoya disease (MMD) have similar transient ischemic attack frequencies compared to patients with chronic cerebral ischemia with other etiologies, but a strong capacity for arteriogenesis and angiogenesis. The mechanisms involved in the upregulation of the arteriogenesis and angiogenesis in MMD still remain unknown. In the present study we investigated if circulating endothelial progenitor cells are increasingly mobilized during MMD.
Twenty MMD patients, 8 patients with atherosclerotic cerebrovascular disease, and 15 healthy individuals were included in this study. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and circulating endothelial progenitor cells were characterized by triple staining using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2. Serum concentrations of vascular endothelial growth factor and granulocyte-macrophage colony-stimulating factor were determined by enzyme-linked immunosorbent assay.
In MMD patients the number of circulating endothelial progenitor cells was significantly higher than in atherosclerotic cerebrovascular disease patients (P<0.002) and healthy controls (P<0.0001). Serum vascular endothelial growth factor concentrations in MMD patients and in atherosclerotic cerebrovascular disease patients were significantly higher compared to those in healthy controls (P<0.0001). Similar findings were observed for granulocyte-macrophage colony-stimulating factor. An inverse correlation between circulating endothelial progenitor cell numbers and serum levels of vascular endothelial growth factor (r=-0.53; P<0,02) was found in the MMD group.
Our results show increased circulating endothelial progenitor cell numbers in MMD, which may play a role in the increased arteriogenesis and angiogenesis in MMD. Moreover, our results suggest that increased circulating endothelial progenitor cell mobilization in MMD may not be entirely mediated by vascular endothelial growth factor or granulocyte-macrophage colony-stimulating factor.
慢性脑缺血会因侧支循环不足导致中风风险升高，这是由动脉生成和血管生成能力不足所致。烟雾病（MMD）患者与其他病因的慢性脑缺血患者相比，短暂性脑缺血发作频率相似，但具有较强的动脉生成和血管生成能力。MMD中动脉生成和血管生成上调所涉及的机制仍不清楚。在本研究中，我们调查了MMD患者体内循环内皮祖细胞是否会被更多地动员起来。
本研究纳入了20例MMD患者、8例动脉粥样硬化性脑血管病患者和15名健康个体。通过Ficoll密度梯度离心法分离外周血单个核细胞，使用抗CD133、CD34和血管内皮生长因子受体-2的抗体进行三重染色来鉴定循环内皮祖细胞。采用酶联免疫吸附测定法测定血管内皮生长因子和粒细胞-巨噬细胞集落刺激因子的血清浓度。
MMD患者循环内皮祖细胞数量显著高于动脉粥样硬化性脑血管病患者（P<0.002）和健康对照组（P<0.0001）。MMD患者和动脉粥样硬化性脑血管病患者的血清血管内皮生长因子浓度显著高于健康对照组（P<0.0001）。粒细胞-巨噬细胞集落刺激因子也有类似发现。在MMD组中，循环内皮祖细胞数量与血管内皮生长因子血清水平呈负相关（r=-0.53；P<0.02）。
我们的结果显示MMD患者循环内皮祖细胞数量增加，这可能在MMD的动脉生成和血管生成增加中起作用。此外，我们的结果表明，MMD患者循环内皮祖细胞动员增加可能并非完全由血管内皮生长因子或粒细胞-巨噬细胞集落刺激因子介导。
