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 journalArticle

Abstract

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
Volume50
Issue number4
Publication statusPublished - Dec 1999

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Physiology

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    Patrignani, P., Sciulli, M. G., Manarini, S., Santini, G., Cerletti, C., & Evangelista, V. (1999). COX-2 is not involved in thromboxane biosynthesis by activated human platelets. Journal of Physiology and Pharmacology, 50(4), 661-667.