title: Cyclooxygenase and prostaglandin synthases in atherosclerosis: recent insights and future perspectives.
abstract: Cyclooxygenase (COX) is the key enzyme in the conversion of arachidonic acid to prostanoids, lipid mediators involved in several physiological and pathological processes. Two COX isoenzymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity, and preferential coupling to upstream and downstream enzymes. Both isoforms play fundamental roles in atherothrombosis; however, whereas the function of COX-1 in this setting is well established, the role of COX-2 remains unclear. Indeed, the intracellular pathways regulating COX-2 induction appear numerous and complicated, varying between cell types and cellular stimulus. In recent years a long series of studies has been performed with the aim of clarifying the role of COX-2 in atherothrombosis, with the major finding that the COX-2 expression pattern in arterial vessels may be associated with either protective or plaque-destabilizing phenotypes according to the downstream synthase that couples with COX-2. In this review we summarize the role of COX-2 as well as the different downstream synthases in atherosclerosis and atherothrombosis. Finally, we briefly review the controversial vascular effects on prostanoid inhibition by COX-2 inhibitors.
authors.affiliation: Italian Society for the Study of Atherosclerosis, Abruzzo Division, Italy. fcipollone@unich.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Cipollone
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cicolini
authors.forename: Marco
authors.initials: M
authors.lastname: Bucci
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D050197:Atherosclerosis / Q000201:enzymology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000096:biosynthesis; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011457:Prostaglandins D / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000096:biosynthesis
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011457:Prostaglandins D; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase