Jaquet Kai, Krause Korff, Tawakol-Khodai Mona, Geidel Stefan, Kuck Karl-Heinz
Department of Cardiology, St. Georg Hospital, Hamburg, Germany.
Microvasc Res. 2002 Sep;64(2):326-33. doi: 10.1006/mvre.2002.2426.
Erythropoietin (Epo) is a hormone regulating proliferation and differentiation of erythroid cells. The hypothesis that hematopoietic and endothelial cells share a common hemangioblast progenitor among others is based on the finding that both cell lineages express cell surface antigens like CD31 and CD34. In this study we investigated the angiogenic potential of recombinant human erythropoietin (rHuEpo) on endothelial cells derived from human adult myocardial tissue. In addition, we compared the angiogenic potential of rHuEpo to that of other cytokines (VEGF, aFGF) and combinations of growth factors. Samples of myocardial tissue (cardiac auricle) were obtained during coronary bypass surgery, embedded in a fibrin gel matrix, and cultured for 21 days. Capillary sprouting was measured with an eye-piece graticule under an inverted-phase contrast microscope. Tube-forming endothelial cells were characterized by immunohistochemistry and RT-PCR. Using a concentration of 2.5 U/ml, we found that rHuEpo stimulates capillary outgrowth up to 220%, compared to the nonstimulated physiological outgrowth. Epo therefore exhibits the same angiogenic potential on endothelial cells in our in vitro assay as VEGF(165) (230% increase). Erythropoietin stimulates capillary outgrowth in an in vitro angiogenesis assay using adult human myocardial tissue. This implies a role of erythropoietin in vasoproliferative processes. rHuEpo may serve as a direct angiogenic substance in patients with ischemic heart disease.
促红细胞生成素（Epo）是一种调节红细胞系细胞增殖和分化的激素。造血细胞和内皮细胞等具有共同的成血管细胞祖细胞这一假说，是基于两种细胞谱系都表达CD31和CD34等细胞表面抗原这一发现。在本研究中，我们调查了重组人促红细胞生成素（rHuEpo）对源自成人人类心肌组织的内皮细胞的血管生成潜力。此外，我们将rHuEpo的血管生成潜力与其他细胞因子（VEGF、aFGF）以及生长因子组合的血管生成潜力进行了比较。在冠状动脉搭桥手术期间获取心肌组织（心耳）样本，将其包埋在纤维蛋白凝胶基质中，并培养21天。在倒置相差显微镜下用目镜测微尺测量毛细血管芽生。通过免疫组织化学和逆转录-聚合酶链反应对形成管腔的内皮细胞进行表征。使用2.5 U/ml的浓度时，我们发现与未刺激的生理性生长相比，rHuEpo可使毛细血管生长增加高达220%。因此，在我们的体外试验中，Epo对内皮细胞表现出与VEGF(165)相同的血管生成潜力（增加230%）。促红细胞生成素在使用成人人类心肌组织的体外血管生成试验中刺激毛细血管生长。这意味着促红细胞生成素在血管增殖过程中发挥作用。rHuEpo可能作为缺血性心脏病患者的直接血管生成物质。
