Role of prostacyclin in the cardiovascular response to thromboxane A2

Bianca Rocca, Y Cheng, Sc Austin, Bh Koller, Tm Coffman, T Grosser, Ja Lawson, Ga Fitzgerald

Risultato della ricerca: Contributo in rivistaArticolo in rivista

692 Citazioni (Scopus)

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 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.
Lingua originaleEnglish
pagine (da-a)539-541
Numero di pagine3
RivistaSCIENCE
Volume296
DOI
Stato di pubblicazionePubblicato - 2002

Keywords

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Animals
  • Carotid Artery Injuries
  • Carotid Artery, Common
  • Cell Division
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Endothelium, Vascular
  • Epoprostenol
  • Humans
  • Isoenzymes
  • Lactones
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Muscle, Smooth, Vascular
  • Naphthalenes
  • Platelet Activation
  • Platelet Aggregation
  • Propionic Acids
  • Prostaglandin-Endoperoxide Synthases
  • Receptors, Epoprostenol
  • Receptors, Prostaglandin
  • Receptors, Thromboxane
  • Sulfones
  • Tetrahydronaphthalenes
  • Thromboxane A2
  • Tunica Intima

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