Article
VEGF mRNA-expression in cells of chronic subdural hematoma fluid and Ang1/Ang2 imbalance in hematoma membranes
VEGF mRNA Expression in Zellen des chronisch subduralen Hämatomes und Ang1/Ang2-Imbalance in der Hämatommembran
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Published: | April 23, 2004 |
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Outline
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Objective
Chronic subdural hematoma (cSDH) is characterized by a tremendously increased concentration of vascular endothelial growth factor (VEGF) in the hematoma fluid which may contribute to ongoing angiogenesis in the hematoma membrane. The current study was conducted to determine the source(s) of the VEGF and identifiy the presence of angiopoietin (ANG)-1 and -2 and their receptor, Tie-2 since the ANG/Tie system is an important factor in regulation of angiogenesis.
Methods
Samples of hematoma fluid and venous blood were obtained intraoperatively from 21 patients, and specimens of hematoma membranes were taken from 14 patients. The distribution of cells in the blood and hematoma fluid of 12 patients was investigated using a blood cell-analyser (Sysmex). The presence of VEGF, Ang-1 and Ang-2 and Tie-2 mRNA was investigated by RT-PCR methodology in the hematoma membranes (n=14), cells isolated from the hematoma fluid and in blood cells (n=12). The VEGF content in the hematoma fluid and plasma was measured using a commercially available ELISA kit.
Results
The VEGF content in the hematoma fluid ranged from 4,300 to 89,650 pg/ml and weakly correlated with the number of neutrophils in the hematoma fluid. The VEGF mRNA-expression (relative to that of GAPDH as housekeeping gene) was 9.3 fold higher in cells obtained from the hematoma fluid than in cells from corresponding blood samples. VEGF mRNA in the hematoma membrane was detectable in 8 of 14 samples only. The mRNA species encoding for Ang-1 and Ang-2 were present in all of the hematoma membrane specimens. However, the balance of Ang1/Ang2 mRNA expression was shifted in favor of Ang-2 (0.4?0.36, mean?SD) compared to normal brain tissue (1.8). In addition, the Tie-2 receptor mRNA was detected in all hematoma membranes analysed.
Conclusions
The present results suggest that the cells floating in the hematoma fluid make a substantial contribution to the high VEGF protein concentration in hematoma fluid. They may, thus, play a crucial role in hematoma enlargement by continuously stimulating generation of new blood vessel formation and increasing vessel permeability in the hematoma membrane. In addition, ongoing angiogenesis in the hematoma membrane appears to be enhanced by an imbalance of Ang-1/-2 mRNA expression which may offer a new approach to antagonize hematoma enlargement.