TY - JOUR
T1 - Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E 2-dependent plaque instability
AU - Cipollone, Francesco
AU - Prontera, Cesaria
AU - Pini, Barbara
AU - Marini, Matteo
AU - Fazia, Maria
AU - De Cesare, Domenico
AU - Iezzi, Annalisa
AU - Ucchino, Sante
AU - Boccoli, Gianfranco
AU - Saba, Vittorio
AU - Chiarelli, Francesco
AU - Cuccurullo, Franco
AU - Mezzetti, Andrea
PY - 2001/8/21
Y1 - 2001/8/21
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Inflammation
KW - Metalloproteinases
KW - Plaque
KW - Prostaglandins
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M3 - Article
C2 - 11514380
AN - SCOPUS:0035928784
VL - 104
SP - 921
EP - 927
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 8
ER -