Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
PLoS One. 2012;7(4):e34717. doi: 10.1371/journal.pone.0034717. Epub 2012 Apr 10.
Thromboangiitis obliterans (TAO, also known as Buerger's disease) is a non-atherosclerotic inflammatory vascular disease that primarily affects arteries in the extremities of young adult smokers. Since the etiology of TAO is still unknown, therapeutic options are limited. Recent attempts in therapeutic angiogenesis have been promising. Therefore, the aim of our study was to evaluate angiogenic processes and factors including circulating progenitor cells in TAO.
METHODOLOGY/PRINCIPAL FINDINGS: TAO patients with critical limb ischemia and age- and gender-matched nonsmokers and smokers without cardiovascular disease (n = 12 in each group) were enrolled in the study. Flow cytometric analysis of peripheral blood showed significantly decreased levels of circulating CD45(dim)CD34(+) progenitor cells in TAO patients and in smokers compared to nonsmokers. In contrast to both control groups, the proportion of CD45(dim)CD34(+) progenitor cells co-expressing VEGF receptor-2 (VEGFR2) was significantly elevated in TAO patients. Enzyme-linked immunosorbent assay (ELISA) of common angiogenic factors (such as VEGF) did not clearly point to pro- or antiangiogenic conditions in serum or plasma of TAO patients. Serum of TAO patients and controls was evaluated in proliferation, migration (scratch assay) and spheroid sprouting assays using human umbilical vein endothelial cells (HUVECs). Serum of TAO patients exhibited a diminished sprouting capacity of HUVECs compared to both control groups. Proliferation and migration of endothelial cells were impaired after treatment with serum of TAO patients.
Levels of circulating progenitor cells were altered in TAO patients compared to healthy nonsmokers and smokers. Furthermore, serum of TAO patients exhibited an antiangiogenic activity (impaired endothelial cell sprouting, migration and proliferation) on endothelial cells, which may contribute to vascular pathology in this patient population.
血栓闭塞性脉管炎（TAO，又称伯格氏病）是一种非动脉粥样硬化性炎症性血管疾病，主要影响年轻成年吸烟者的四肢动脉。由于 TAO 的病因仍不清楚，治疗选择有限。最近在治疗性血管生成方面的尝试取得了可喜的成果。因此，我们的研究目的是评估 TAO 中的血管生成过程和因素，包括循环祖细胞。
方法/主要发现：我们招募了 12 例有严重肢体缺血的 TAO 患者、年龄和性别匹配的不吸烟和无心血管疾病的吸烟者（每组 12 例）。外周血流式细胞术分析显示，TAO 患者和吸烟者的循环 CD45(dim)CD34(+)祖细胞水平明显低于不吸烟者。与所有对照组相比，TAO 患者中表达血管内皮生长因子受体-2 (VEGFR2)的 CD45(dim)CD34(+)祖细胞的比例明显升高。酶联免疫吸附试验（ELISA）检测常见的血管生成因子（如 VEGF）并未明确指出 TAO 患者血清或血浆中存在促血管生成或抗血管生成的条件。我们使用人脐静脉内皮细胞（HUVEC）评估了 TAO 患者和对照组的血清在增殖、迁移（划痕试验）和球体发芽试验中的作用。与两组对照组相比，TAO 患者的血清显示出 HUVEC 发芽能力减弱。TAO 患者血清处理后的内皮细胞增殖和迁移受损。
与健康不吸烟者和吸烟者相比，TAO 患者的循环祖细胞水平发生了改变。此外，TAO 患者的血清表现出抗血管生成活性（内皮细胞发芽、迁移和增殖受损），这可能导致该患者群体的血管病理学改变。
