Role of Prostacyclin in the Cardiovascular Response to Thromboxane A2
Abstract
Thromboxane (Tx) A2 is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI2) is a vasodilator that inhibits platelet function. Here we show that injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the PGI2receptor (IP) but are depressed in mice genetically deficient in the TxA2 receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI2 modulates platelet-vascular interactions in vivo and specifically limits the response to TxA2. This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), inhibit PGI2 but not TxA2.
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Supplementary Material
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We wish to thank P. McNamara and R. D. Rudic for advice and encouragement. We also thank S. Segel and H. Li for technical assistance. Supported in part by grants from Servier and the National Institutes of Health (HL 54500 and HL 62250). All procedures were considered and approved by Institutional Animal Care and Usage Committee of the University of Pennsylvania.
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Science
Volume 296 | Issue 5567
19 April 2002
19 April 2002
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Received: 5 December 2001
Accepted: 28 February 2002
Published in print: 19 April 2002
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