Cyclooxygenase and prostaglandin synthases: roles in plaque stability and instability in humans.
OBJECTIVE
Cyclooxygenase (COX) is the key enzyme of the arachidonic acid metabolism and it plays a major role in development of both coronary and cerebrovascular disease. In this review, we will analyze the role of COX and prostaglandin synthases in plaque stability.


RESULTS
As shown by experimental studies based on biochemical measurement of eicosanoid biosynthesis and by the results of clinical trials, COX plays a key role in plaque evolution. Two COX-isozymes have been identified, COX-1 and COX-2, with different tissue distribution, substrate specificity, regulatory mechanism and susceptibility to drugs inhibition. Whereas, the role of platelet COX-1 in acute coronary syndrome and ischemic stroke is definitely established through several large clinical studies with aspirin, the role of COX-2 in these settings is still under investigation because this enzyme was characterized only recently and its inhibitors (coxibs) became available only in 1998. Recent findings seem to suggest that functional consequences of COX-2 expression and inhibition in different clinical settings may depend on different expression of upstream and downstream receptors as well as by genetic polymorphism.


CONCLUSIONS
COX-2 and prostaglandin synthases and their modulation play a major role in plaque homeostasis and in its clinical manifestations.
Santovito
Donato
D
Italian Society for the Study of Atherosclerosis, Abruzzo section, Chieti, Italy.
Mezzetti
Andrea
A
Cipollone
Francesco
F
D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D000071876:Prostaglandin-E Synthases
D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases