Los M, Aarsman C J, Terpstra L, Wittebol-Post D, Lips C J, Blijham G H, Voest E E
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Ann Oncol. 1997 Oct;8(10):1015-22. doi: 10.1023/a:1008213320642.
Von Hippel Lindau disease (VHL) is a rare autosomal dominant inherited disorder characterized by highly vascularized tumors in various organs. The abundant presence of endothelial cells in VHL tumors strongly suggest a role of the VHL tumor suppressor gene in the regulation of angiogenesis. Recently, in vitro studies have shown that the VHL tumor suppressor gene regulates the expression of vascular endothelial growth factor (VEGF). We investigated whether VHL patiens have increased levels of VEGF in their body fluids.
The concentration of VEGF was measured in fluid of the anterior chamber of the eye, serum, urine, and fluid from renal cysts of VHL patients and unaffected individuals by ELISA. In addition, levels of basic fibroblast growth factor (bFGF), interleukin-8 (IL-8) and endothelin-1 (ET-1) were measured in urine and serum of VHL patients and control subjects.
In 80% of the VHL patients VEGF was detectable in aqueous fluid of the anterior chamber of their eyes. A strong positive correlation (r = 0.90) was found between the age of VHL patients and ocular VEGF concentrations. At comparable age, VEGF levels in ocular fluid of VHL patients were significantly higher (P < 0.001) than in unaffected subjects. No correlation was found between VEGF concentration and the presence of retinal angiomas. A 10 and 16 fold increase of VEGF concentration was seen in fluid from two independent VHL-related cysts as compared with VEGF serum levels of the same patient. The mean concentration of VEGF in serum of VHL patients (n = 15) (319 +/- 84 pg/ml) was higher than in matched controls (238 +/- 68 pg/ml; P = NS). The mean concentration of VEGF in urine of VHL patients (128 +/- 36 pg/ml) was lower than in matched controls (183 +/- 25 pg/ml; P = NS). Concentrations of VEGF did not correlate with the presence of VHL-related tumors. No differences were observed between concentrations of bFGF, IL-8 and ET-1 in serum and urine of VHL patients and matched controls.
These findings support a role for the VHL tumor suppressor gene in the in vivo regulation of VEGF.
冯·希佩尔-林道病（VHL）是一种罕见的常染色体显性遗传疾病，其特征是各器官出现高度血管化肿瘤。VHL肿瘤中内皮细胞大量存在，强烈提示VHL肿瘤抑制基因在血管生成调节中发挥作用。最近，体外研究表明，VHL肿瘤抑制基因调节血管内皮生长因子（VEGF）的表达。我们研究了VHL患者体液中VEGF水平是否升高。
通过酶联免疫吸附测定法（ELISA）测量VHL患者和未受影响个体的眼前房液、血清、尿液及肾囊肿液中VEGF的浓度。此外，还测量了VHL患者和对照受试者尿液及血清中碱性成纤维细胞生长因子（bFGF）、白细胞介素-8（IL-8）和内皮素-1（ET-1）的水平。
80%的VHL患者眼前房液中可检测到VEGF。VHL患者年龄与眼内VEGF浓度之间存在强正相关（r = 0.90）。在可比年龄下，VHL患者眼内液中的VEGF水平显著高于未受影响的受试者（P < 0.001）。VEGF浓度与视网膜血管瘤的存在无相关性。与同一患者的VEGF血清水平相比，两个独立的与VHL相关囊肿液中的VEGF浓度分别升高了10倍和16倍。VHL患者（n = 15）血清中VEGF的平均浓度（319 ± 84 pg/ml）高于匹配的对照组（238 ± 68 pg/ml；P = 无显著性差异）。VHL患者尿液中VEGF的平均浓度（128 ± 36 pg/ml）低于匹配的对照组（183 ± 25 pg/ml；P = 无显著性差异）。VEGF浓度与VHL相关肿瘤的存在无相关性。VHL患者与匹配对照组血清和尿液中bFGF、IL-8和ET-1的浓度无差异。
这些发现支持VHL肿瘤抑制基因在体内对VEGF的调节作用。
