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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
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Animals
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Bridged Bicyclo Compounds, Heterocyclic
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Cell Movement / drug effects
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Cell Movement / physiology
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Cells, Cultured
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Cornea / blood supply*
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology*
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Dinoprost / pharmacology
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Dinoprostone / pharmacology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / physiology*
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Fatty Acids, Unsaturated
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Fibroblast Growth Factor 2 / pharmacology
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Fibroblast Growth Factors / pharmacology
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Humans
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Hydrazines / pharmacology
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Isoenzymes / metabolism*
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Membrane Proteins
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Mice
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Mice, Inbred C57BL
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Microcirculation
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Neovascularization, Pathologic / physiopathology
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Neovascularization, Physiologic / drug effects
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Neovascularization, Physiologic / physiology*
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Renal Circulation
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Tetradecanoylphorbol Acetate / pharmacology
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Thromboxane A2 / physiology*
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Fatty Acids, Unsaturated
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Hydrazines
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Isoenzymes
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Membrane Proteins
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Fibroblast Growth Factor 2
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Thromboxane A2
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Fibroblast Growth Factors
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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SQ 29548
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Dinoprost
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone
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Tetradecanoylphorbol Acetate