Cyclooxygenase-2 inhibition: vascular inflammation and cardiovascular risk

The inducible isoform of cyclooxygenase-2 (COX-2) plays a role in pathophysiologic processes like inflammation and pain but is also constitutively expressed in tissues such as the kidney or vascular endothelium, where it exerts important physiologic functions. Although much evidence exists that implicates COX-2 in atherosclerosis, its role in this setting remains substantially uncertain. This observation is also confirmed by the results of clinical trials of selective COX-2 inhibitors. Treatment with these drugs, developed with the assumption that they would be as effective as nonselective COX inhibitors but without their gastrointestinal side effects, has been reported to be associated with an increased cardiovascular risk. In this article, we review the pattern of expression of COX-2 in the cellular players of atherothrombosis, its role as a determinant of plaque vulnerability, and the vascular effects on prostanoid inhibition by COX-2 inhibitors.