Thromboxane A(2) is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis

Cyclooxygenase-2 (COX-2) inhibitors reduce angiogenic responses to a variet y of stimuli, suggesting that products of COX-2 may mediate critical steps. Here, we show that thromboxane A, TXA(2) is one of several eicosanoid prod ucts generated by activated human microvascular endothelial cells. Selectiv e COX-2 antagonists inhibit TXA(2) production, endothelial migration, and f ibroblast growth factor-induced corneal angiogenesis, Endothelial migration and corneal angiogenesis are similarly inhibited by a TXA(2) receptor anta gonist, SQ29548, A TXA(2) agonist, U46619, reconstitutes both migration and angiogenesis responses under COX-2-inhibited conditions, These findings id entify TXA(2) as a COX-2 product that functions as a critical intermediary of angiogenesis.