Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis

Cancer Res. 1999 Sep 15;59(18):4574-7.

Abstract

Cyclooxygenase-2 (COX-2) inhibitors reduce angiogenic responses to a variety of stimuli, suggesting that products of COX-2 may mediate critical steps. Here, we show that thromboxane A2 (TXA2) is one of several eicosanoid products generated by activated human microvascular endothelial cells. Selective COX-2 antagonists inhibit TXA2 production, endothelial migration, and fibroblast growth factor-induced corneal angiogenesis. Endothelial migration and corneal angiogenesis are similarly inhibited by a TXA2 receptor antagonist, SQ29548. A TXA2 agonist, U46619, reconstitutes both migration and angiogenesis responses under COX-2-inhibited conditions. These findings identify TXA2 as a COX-2 product that functions as a critical intermediary of angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Cornea / blood supply*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dinoprost / pharmacology
  • Dinoprostone / pharmacology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Fatty Acids, Unsaturated
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factors / pharmacology
  • Humans
  • Hydrazines / pharmacology
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation
  • Neovascularization, Pathologic / physiopathology
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Renal Circulation
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thromboxane A2 / physiology*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Fatty Acids, Unsaturated
  • Hydrazines
  • Isoenzymes
  • Membrane Proteins
  • Fibroblast Growth Factor 2
  • Thromboxane A2
  • Fibroblast Growth Factors
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • SQ 29548
  • Dinoprost
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Tetradecanoylphorbol Acetate