Irmak Ster, Oliveira-Ferrer Leticia, Singer Bernhard B, Ergün Süleyman, Tilki Derya
Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, D-45147 Essen, Germany.
Exp Cell Res. 2009 Nov 1;315(18):3201-9. doi: 10.1016/j.yexcr.2009.07.024. Epub 2009 Aug 3.
The acute phase protein orosomucoid (ORM), also known as alpha1-acid glycoprotein (AGP), is found to be increased in infection, inflammation and cancer. Recently, we demonstrated that ORM is produced by endothelial cells and detectable in urine samples of patients with bladder cancer. However, it was not clarified yet whether ORM plays a role in new vessel formation. To this aim we performed overexpression and gene silencing for ORM in human microvascular endothelial cells (HDMECs). ORM purified from human plasma was used individually or in combination with VEGF-A in endothelial tube formation, migration and proliferation assay. The in vivo effect of ORM in angiogenesis was studied using the chicken chorionallantois membrane (CAM) with subsequent counting of blood vessels on histological sections from the stimulated areas of CAM tissue. Our data show that ORM alone enhances migration but not proliferation of HDMECs. ORM alone does not induce endothelial tubes in vitro but simultaneous application of ORM with VEGF-A increases the number and the network of VEGF-A-induced endothelial tubes. Remarkably, ORM alone induces new vessel formation in vivo using CAM assay and supports the VEGF-A-induced new vessel formation in this assay. Taken together, our results let assume that ORM has pro-angiogenic properties and supports the angiogenic effect of VEGF-A. Thus, ORM seems to be involved in the regulation of angiogenesis.
急性期蛋白血清类黏蛋白（ORM），也称为α1-酸性糖蛋白（AGP），在感染、炎症和癌症中会升高。最近，我们发现ORM由内皮细胞产生，并且在膀胱癌患者的尿液样本中可检测到。然而，ORM是否在新血管形成中发挥作用尚不清楚。为此，我们在人微血管内皮细胞（HDMECs）中对ORM进行了过表达和基因沉默实验。从人血浆中纯化的ORM单独使用或与VEGF-A联合用于内皮管形成、迁移和增殖实验。使用鸡绒毛尿囊膜（CAM）研究ORM在体内对血管生成的影响，随后对CAM组织刺激区域的组织切片上的血管进行计数。我们的数据表明，单独的ORM可增强HDMECs的迁移，但不影响其增殖。单独的ORM在体外不诱导内皮管形成，但与VEGF-A同时应用可增加VEGF-A诱导的内皮管的数量和网络。值得注意的是，单独使用ORM通过CAM实验可在体内诱导新血管形成，并在该实验中支持VEGF-A诱导的新血管形成。综上所述，我们的结果表明ORM具有促血管生成特性，并支持VEGF-A的血管生成作用。因此，ORM似乎参与了血管生成的调节。
