Role of prostacyclin in the cardiovascular response to thromboxane A2.

Published

Journal Article

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 PGI2 receptor (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.

Full Text

Duke Authors

Cited Authors

  • Cheng, Y; Austin, SC; Rocca, B; Koller, BH; Coffman, TM; Grosser, T; Lawson, JA; FitzGerald, GA

Published Date

  • April 19, 2002

Published In

Volume / Issue

  • 296 / 5567

Start / End Page

  • 539 - 541

PubMed ID

  • 11964481

Pubmed Central ID

  • 11964481

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1068711

Language

  • eng

Conference Location

  • United States