title: Modulation of the expression of vascular endothelial growth factor in human fibroblasts.
abstract: 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.
authors.affiliation: 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
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.forename: Eslam
authors.initials: E
authors.lastname: El-Hammady
authors.forename: Adnan
authors.initials: A
authors.lastname: Munkarah
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bieber
authors.forename: Ghassan
authors.initials: G
authors.lastname: Saed
mesh_terms: 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*
chemical_list: 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