Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:646-655
© 1999 American Heart Association, Inc.
Original Contributions |
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
From the Departments of Histochemistry (J.M.P.), Cardiology (C.S.R.B., R.J.C.H.), and Infectious Diseases (T.J.E.), Imperial College School of Medicine, Hammersmith Hospital Campus and Heart Science Center (A.P., M.H.Y.), Imperial College School of Medicine, Harefield Hospital Campus, London, UK; and the Institut National de la Sante et de la Recherche Medicale (J.M.), Paris, and the C.E.A. (C.C.), Service de Pharmacolog et d'Immunologie, Saclay, France.
Correspondence to Dr C.S.R. Baker, Imperial College of Science, Technology and Medicine, Department of Cardiology, Hammersmith Hospital, Du Cane Road, London, W12 ONN UK. E-mail cbaker{at}rpms.ac.uk
Abstract—Inflammation appears to have a major role in the development of atherosclerotic lesions affecting native and transplanted coronary arteries. The subsequent 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 oxide 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 formation of peroxynitrite in the case of nitric oxide and involve "cross talk" between the two enzyme systems. This study aimed to investigate native and transplant atherosclerosis for the presence and distribution of Cox-2 and iNOS. Immunocytochemical studies were performed on atherosclerotic lesions from patients with native (n=12) and transplant (n=5) coronary disease by using antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of peroxynitrite production). Control tissue was obtained from unused donor hearts 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, including those of the vasa vasorum. Nitrotyrosine was found in the same distribution as that of iNOS and was colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native and transplant atherosclerosis, possibly allowing for interaction between the enzymes and suggesting an alternative mechanism for the benefits of aspirin via inhibition of Cox-2 activity.
Key Words: cyclooxygenase-2 • inducible nitric oxide synthase • atherosclerosis • transplant atherosclerosis • inflammation
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