COX-2 is not involved in thromboxane biosynthesis by activated human platelets

Paola Patrignani, M. G. Sciulli, S. Manarini, G. Santini, C. Cerletti, V. Evangelista

Research output: Contribution to journalArticlepeer-review


The occurrence of aspirin resistance has been inferred by the assessment of platelet aggregation ex vivo in patients with ischemic vascular syndromes taking aspirin. Since aspirin is a weak inhibitor of the inducible isoform of prostaglandin H synthase (COX-2), it was suggested that COX-2 may play a role in aspirin resistance. However the cellular source(s) of COX-2 possibly responsible for aspirin resistance remains unknown. Recently, the expression of the inducible isoform of COX-2 in circulating human platelets was reported. To investigate the possible contribution of COX-2 expression in platelet thromboxane (TX) biosynthesis, we have compared the inhibitory effects of NS-398 and aspirin, selective inhibitors of COX-2 and COX-1, respectively, on prostanoid biosynthesis by thrombin-stimulated platelets vs lipopolysaccharide (LPS)-stimulated monocytes (expressing high levels of COX- 2) isolated from whole blood of healthy subjects. NS-398 was 180-fold more potent in inhibiting monocyte COX-2 activity than platelet TXB2 production. In contrast, aspirin (55 μmol/L) largely suppressed platelet TXB2 production without affecting monocyte COX-2 activity. By using specific Western blot techniques, we failed to detect COX-2 in platelets while COX-1 was readily detectable. Our results argue against the involvement of COX-2 in TX biosynthesis by activated platelets and consequently dispute platelet COX- 2 expression as an important mechanism of aspirin resistance.

Original languageEnglish
Pages (from-to)661-667
Number of pages7
JournalJournal of Physiology and Pharmacology
Issue number4
Publication statusPublished - Dec 1999


  • Aspirin
  • COX-1
  • COX-2
  • Platelets
  • Thromboxane

ASJC Scopus subject areas

  • Pharmacology
  • Physiology

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