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

Daniel TO, Liu H, Morrow JD, Crews BC, Marnett LJ
Cancer Res. 1999 59 (18): 4574-7

PMID: 10493510

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.

MeSH Terms (28)

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

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