Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E 2-dependent plaque instability

Francesco Cipollone, Cesaria Prontera, Barbara Pini, Matteo Marini, Maria Fazia, Domenico De Cesare, Annalisa Iezzi, Sante Ucchino, Gianfranco Boccoli, Vittorio Saba, Francesco Chiarelli, Franco Cuccurullo, Andrea Mezzetti

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Studies have implicated a role for prostaglandin (PG) E 2-dependent matrix metalloproteinase (MMP) biosynthesis in the rupture of atherosclerotic plaque. Cyclooxygenase-2 (COX-2) and PGE synthase (PGES) are coregulated in nucleated cells by inflammatory stimuli. The aim of this study was to characterize the expression of COX-2 and PGES in carotid plaques and to correlate it with the extent of inflammatory infiltration and MMP activity and with clinical features of patients' presentation. Methods and Results - Plaques were obtained from 50 patients undergoing carotid endarterectomy and divided into 2 groups (symptomatic and asymptomatic) according to clinical evidence of recent transient ischemic attack or stroke. Plaques were analyzed for COX-2, PGES, MMP-2, and MMP-9 by immunocytochemistry and Western blot, whereas zymography was used to detect MMP activity. Immunocytochemistry was used to identify CD68+ macrophages, CD3+ T lymphocytes, and HLA-DR+ cells. The percentage of macrophage-rich areas was larger (P2. Conclusions - This study demonstrates the colocalization of COX-2 and PGES in symptomatic lesions and provides evidence that synthesis of COX-2 and PGES by activated macrophages is associated with acute ischemic syndromes, possibly through metalloproteinase-induced plaque rupture.

Original languageEnglish
Pages (from-to)921-927
Number of pages7
JournalCirculation
Volume104
Issue number8
Publication statusPublished - Aug 21 2001

Keywords

  • Atherosclerosis
  • Inflammation
  • Metalloproteinases
  • Plaque
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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