Inflammation plays a central role in the development of atherosclerotic disease, from the early phases of lesion formation to plaque disruption, the main underlying cause of acute ischemic syndromes. Arachidonic acid metabolism is implicated in the pathophysiology of ischemic syndromes affecting the coronary or cerebrovascular territory, as demonstrated by biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. In particular, much attention has been focused on the pathway catalyzed by cyclooxygenase (COX), which leads to the generation of a variety of lipid mediators known as prostanoids. Two COX isozymes 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. Whereas the role of platelet COX-1 in acute ischemic diseases is established, the role of COX-2 in atherothrombosis remains unclear. In this article, we summarize the findings from our group suggesting a crucial role for COX-2 in modulating atherosclerotic plaque stability or instability, according to the variable expression of upstream and downstream enzymes in the prostanoid biosynthesis.
