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Elevated ocular levels of vascular endothelial growth factor in patients with von Hippel-Lindau disease.

AbstractBACKGROUND:
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.
PATIENTS AND METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
These findings support a role for the VHL tumor suppressor gene in the in vivo regulation of VEGF.
AuthorsM Los, C J Aarsman, L Terpstra, D Wittebol-Post, C J Lips, G H Blijham, E E Voest
JournalAnnals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 8 Issue 10 Pg. 1015-22 (Oct 1997) ISSN: 0923-7534 [Print] England
PMID9402176 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Endothelial Growth Factors
  • Endothelin-1
  • Interleukin-8
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
Topics
  • Adult
  • Anterior Chamber (metabolism)
  • Body Fluids (metabolism)
  • Endothelial Growth Factors (blood, metabolism, urine)
  • Endothelin-1 (metabolism)
  • Female
  • Fibroblast Growth Factor 2 (metabolism)
  • Humans
  • Interleukin-8 (metabolism)
  • Lymphokines (blood, metabolism, urine)
  • Male
  • Middle Aged
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • von Hippel-Lindau Disease (blood, metabolism, urine)

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