Cyclooxygenase and prostaglandin synthases: roles in plaque stability and instability in humans.

Purpose of review: 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. Recent findings: 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. Summary: COX-2 and prostaglandin synthases and their modulation play a major role in plaque homeostasis and in its clinical manifestations