Modulation of the expression of vascular endothelial growth factor in human fibroblasts.
OBJECTIVE
To examine the up-regulation of vascular endothelial growth factor (VEGF) expression by hypoxia, a crucial event leading to neovascularization, as the reduction in VEGF expression may facilitate minimization of adhesion development.


METHODS
Prospective experimental study.


METHODS
University medical center.


METHODS
Five patients with adhesions undergoing laparotomy with excision of adhesions and normal peritoneum.


METHODS
Adhesion and normal peritoneal fibroblasts were treated with dichloroacetic acid (DCA) or NS-398 (a cyclooxygenase-2 [COX-2] inhibitor) for 24 to 48 hours.


METHODS
A real-time reverse transcriptase polymerase chain reaction (RT-PCR) to quantify relative changes in mRNA levels of VEGF from each treatment.


RESULTS
In both normal peritoneal and adhesion fibroblasts, VEGF mRNA was present with statistically significantly higher levels in adhesion fibroblasts (32%). The DCA treatment resulted in a statistically significant decrease in VEGF mRNA levels in adhesion (20%) and normal peritoneal (18%) fibroblasts. The NS-398 treatment resulted in a statistically significant decrease in VEGF mRNA levels in adhesion (25%) and normal peritoneal (16%) fibroblasts.


CONCLUSIONS
Stimulation of aerobic metabolism by DCA or inhibition of COX-2 by NS-398 reduces VEGF expression. Angiogenesis, which is an integral component in the development of dense vascular adhesions, may be reduced by either COX-2 inhibitors or stimulation of aerobic metabolism by DCA.
Diamond
Michael P
MP
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University/Detroit Medical Center, Detroit, MI 48201, USA. mdiamond@med.wayne.edu
El-Hammady
Eslam
E
Munkarah
Adnan
A
Bieber
Eric J
EJ
Saed
Ghassan
G
D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009578:Nitrobenzenes / Q000494:pharmacology; D010537:Peritoneum / Q000166:cytology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D013449:Sulfonamides / Q000494:pharmacology; D000267:Tissue Adhesions / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D003999:Dichloroacetic Acid