Significant roles of inducible cyclooxygenase (COX)-2 in angiogenesis in rat sponge implants

Jpn J Pharmacol. 1997 Oct;75(2):105-14. doi: 10.1254/jjp.75.105.


Angiogenesis in rat sponge implants, as determined from the concentration of hemoglobin in the sponge granuloma tissues, was gradually increased over a 14-day experimental period. The inducible cyclooxygenase COX-2 was detected in the sponge granuloma tissues at day 4 by Western blot analysis using specific mouse COX-2 antibody. Angiogenesis in the sponge implants was enhanced by daily topical injections of human recombinant basic fibroblast growth factor (bFGF) or human recombinant epidermal growth factor (EGF) (100 or 1000 ng/sponge/day) for 4 days. These treatments clearly enhanced the expression of COX-2 in the sponge granuloma tissues. In immunohistochemical studies, COX-2-positive staining was mainly observed in the endothelial cells of the neovasculature and in the fibroblasts of the granuloma capsule. Administration of the selective COX-2 inhibitor NS-398 (p.o., 3 mg/kg, 3 times a day) for 14 days significantly inhibited the angiogenesis. The angiogenesis enhanced with bFGF or EGF (day 4) was inhibited by administration of indomethacin or NS-398, both in the above regimen, and fell to the level obtained without growth factor treatment. These results suggest that COX-2 induced in the sponge granuloma tissues may participate in neovascularization through prostaglandin formation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cyclooxygenase 2
  • Enzyme Inhibitors / pharmacology
  • Granuloma, Foreign-Body / enzymology*
  • Granuloma, Foreign-Body / metabolism
  • Granuloma, Foreign-Body / pathology
  • Hemoglobins / metabolism
  • Immunohistochemistry
  • Isoenzymes / biosynthesis*
  • Isoenzymes / physiology
  • Male
  • Neovascularization, Pathologic / enzymology*
  • Neovascularization, Pathologic / metabolism
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / physiology
  • Rats
  • Rats, Sprague-Dawley


  • Enzyme Inhibitors
  • Hemoglobins
  • Isoenzymes
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases