title: Differential suppression of vascular permeability and corneal angiogenesis by nonsteroidal anti-inflammatory drugs.
abstract: OBJECTIVE
  Angiogenesis, the formation of new capillary blood vessels, is an essential biological process under physiological conditions, including embryonic development, reproduction, and wound repair. Under pathologic conditions, this process plays a critical role in a variety of diseases such as cancer, rheumatoid arthritis, atherosclerosis, endometriosis, diabetic retinopathy, and age-related macular degeneration. The purpose of this study was to examine the effects of cyclooxygenase inhibitors on basic fibroblast growth factor (bFGF)- and vascular endothelial growth factor (VEGF)-mediated ocular neovascularization and permeability.
  
  
  METHODS
  A modified Miles vascular permeability assay was used to examine VEGF-induced vascular hyperpermeability, and the mouse corneal model of angiogenesis was used to compare the efficacy of systemic treatment with different nonsteroidal anti-inflammatory drugs (NSAIDs) on bFGF- and VEGF-induced angiogenesis.
  
  
  RESULTS
  The authors demonstrated that systemic application of most NSAIDs, but not acetaminophen, blocked VEGF-induced permeability in mice. However, systemic treatment of mice with NSAIDs resulted in the differential inhibition of bFGF-induced (5%-57%) and VEGF-induced (3%-66%) corneal angiogenesis. The selective COX-2 inhibitors were more effective at suppressing bFGF-induced angiogenesis than VEGF-induced angiogenesis.
  
  
  CONCLUSIONS
  Though most NSAIDS are effective at suppressing vascular leak, there exists a differential efficacy at suppressing the angiogenic response of specific cytokines such as bFGF and VEGF.
authors.affiliation: Departments of Surgery, Harvard Medical School, Children's Hospital Boston, Boston, Massachusetts, USA.
authors.forename: Pouya
authors.initials: P
authors.lastname: Pakneshan
authors.forename: Amy E
authors.initials: AE
authors.lastname: Birsner
authors.forename: Irit
authors.initials: I
authors.lastname: Adini
authors.forename: Christian M
authors.initials: CM
authors.lastname: Becker
authors.forename: Robert J
authors.initials: RJ
authors.lastname: D'Amato
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D003315:Cornea / Q000098:blood supply* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000082:Acetaminophen