Relationship between cyclooxygenase-2 inhibition and thrombogenesis.
Recently there has been considerable interest in the role of cyclooxygenase-2 (COX-2) in thrombosis and myocardial infarction. A large number of clinical and basic studies have focused on whether COX-2 inhibitors can induce a prothrombotic disorder and increase the risk of cardiovascular thrombosis. This article reviews (1) the roles of COX-2 in the metabolism of prostaglandins; (2) the influence of COX-2 inhibition in the platelet aggregation and the antithrombotic function of vascular endothelium; (3) the roles of COX-2 inhibition in atherothrombosis; and (4) clinical trials that examine COX-2 inhibition in relationship to the risk of myocardial infarction. Based on the published data, this review suggests that COX-2 plays varying and sometimes conflicting roles in thrombogenesis, in prostaglandins' metabolism of endothelium in healthy or dysfunctional conditions, and in atherothrombosis. Future investigations under different pathologic conditions are needed to fully understand the net effect of COX-2 inhibition on thrombogenesis. The roles of COX-2 in the pathophysiologic process of cardiovascular thrombosis are diverse and controversial, and need to be further studied to guide clinical practice.
Dai
Wangde
W
The Heart Institute, Good Samaritan Hospital, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, CA 90017, USA.
Kloner
Robert A
RA
D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000009:adverse effects* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008565:Membrane Proteins; D009203:Myocardial Infarction / Q000139:chemically induced; D010974:Platelet Aggregation; D011451:Prostaglandin-Endoperoxide Synthases / Q000009:adverse effects* / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D012307:Risk Factors; D013927:Thrombosis / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases