Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages

Inflammation appears to have a major role in the development of atheroscler otic lesions affecting native and transplanted coronary arteries. The subse quent risk of plaque rupture and acute ischemic events correlates with the degree of inflammation and may be modified by aspirin, an anti-inflammatory cyclooxygenase inhibitor. Cyclooxygenase-2 (Cox-2) and inducible nitric ox ide synthase (iNOS) are involved in the inflammatory response via the rapid and exaggerated production of prostanoids and nitric oxide, both of which may have proatherosclerotic effects. These effects may be mediated by the f ormation of peroxynitrite in the case of nitric oxide and involve "cross ta lk" between the two enzyme systems. This study aimed to investigate native and transplant atherosclerosis for the presence and distribution of Cox-2 a nd iNOS. Immunocytochemical studies were performed on atherosclerotic lesio ns from patients with native (n = 12) and transplant (n = 5) coronary disea se by using antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of p eroxynitrite production). Control tissue was obtained from unused donor hea rts and at the time of autopsy. Cox-2 and iNOS colocalized predominantly in macrophages/foam cells in both types of atherosclerosis. Cox-2 expression was also detected in medial smooth muscle cells and endothelial cells, incl uding these of the vasa vasorum. Nitrotyrosine was found in the same distri bution as that of iNOS and was colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native and transplant atherosclerosis, possibl y allowing for interaction between the enzymes and suggesting an alternativ e mechanism for the benefits of aspirin via inhibition of Cox-2 activity.