Details

Autor(en) / Beteiligte

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

Titel

Overexpression of Functionally Coupled Cyclooxygenase-2 and Prostaglandin E Synthase in Symptomatic Atherosclerotic Plaques as a Basis of Prostaglandin E 2 -Dependent Plaque Instability

Ist Teil von

• Circulation (New York, N.Y.), 2001-08, Vol.104 (8), p.921-927

Erscheinungsjahr

2001

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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 ( P <0.0001) in symptomatic plaques. COX-2, PGES, and MMPs were detected in all specimens; enzyme concentration, however, was significantly higher in symptomatic plaques. COX-2, PGES, and MMPs were especially noted in shoulders of symptomatic plaques, colocalizing with HLA-DR+ macrophages. All symptomatic plaques contained activated forms of MMPs. Finally, inhibition of COX-2 by NS-398 was accompanied by decreased production of MMPs that was reversed by PGE 2 . 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.