Cyclooxygenase and prostaglandin synthases in atherosclerosis: recent insights and future perspectives.
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.
Cipollone
Francesco
F
Italian Society for the Study of Atherosclerosis, Abruzzo Division, Italy. fcipollone@unich.it
Cicolini
Giancarlo
G
Bucci
Marco
M
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
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