title: Novel determinants of plaque instability.
abstract: Arachidonic acid metabolism plays an important role in acute ischemic syndromes affecting the coronary or cerebrovascular territory, as reflected by biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. Two cyclooxygenase (COX)-isozymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, preferential coupling to upstream and downstream enzymes and susceptibility to inhibition by the extremely heterogeneous class of COX-inhibitors. While the role of platelet COX-1 in acute coronary syndromes and ischemic stroke is firmly established through approximately 20 years of thromboxane metabolite measurements and aspirin trials, the role of COX-2 expression and inhibition in atherothrombosis is substantially uncertain, because the enzyme was first characterized in 1991 and selective COX-2 inhibitors became commercially available only in 1998. In this review, we discuss the pattern of expression of COX-2 in the cellular players of atherothrombosis, its role as a determinant of plaque 'vulnerability,' and the clinical consequences of COX-2 inhibition. Recent studies from our group suggest that variable expression of upstream and downstream enzymes in the prostanoid biosynthetic cascade may represent important determinants of the functional consequences of COX-2 expression and inhibition in different clinical settings.
authors.affiliation: Atherosclerosis Prevention Center and Clinical Research Center, 'G. d'Annunzio' University Foundation, 'G. d'Annunzio' University of Chieti, Chieti, Italy. fcipollone@unich.it
authors.forename: F
authors.initials: F
authors.lastname: Cipollone
authors.forename: M
authors.initials: M
authors.lastname: Fazia
authors.forename: A
authors.initials: A
authors.lastname: Mezzetti
mesh_terms: D050197:Atherosclerosis / Q000473:pathology*; D006801:Humans; D007511:Ischemia; D012421:Rupture / Q000209:etiology