Affiliation:
1. From the Department of Applied Pharmacology (D.B.-B., S.W.L.) and Department of Thoracic Medicine (E.-B.H., R.N.), National Heart and Lung Institute, Imperial College of Science, Technology and Medicine; and Department of Cardiothoracic Surgery (J.R.P.) and Department of Anaesthetics and Critical Care Medicine (J.A.M.), Royal Brompton National Heart and Lung Hospital, London, UK.
Abstract
Abstract
Within vessels, cyclooxygenase (COX) is expressed constitutively (COX-1) in endothelial cells where its production of prostacyclin is thought to contribute to the maintenance of vascular integrity. Recently, a novel isoform of COX, COX-2, has been described that is induced in animal arterial vessels after physical damage or exposure to proinflammatory cytokines. However, induction of COX-2 in human vessels has not been characterized. Moreover, the relative ability of arteries and veins to express COX-2 has not been addressed. Thus, we have compared the ability of segments of human saphenous vein and internal mammary artery, obtained from the same patient, to express COX-2 activity and mRNA after organ culture in the presence and absence of interleukin-1β. COX-2 metabolites, measured by radioimmunoassay, were released by both the internal mammary artery and saphenous vein in the following rank order: prostaglandin E
2
≥prostacyclin thromboxane A
2
. Inclusion of interleukin-1β in the culture medium increased the release of prostanoids by the saphenous vein but not by the internal mammary artery. However, the selective COX-2 inhibitor NS-398 significantly attenuated prostacyclin release from both tissues. Northern blot analysis showed no detectable COX-2 mRNA in freshly prepared saphenous vein or internal mammary artery. In contrast, after 48 hours in organ culture, low levels of COX-2 mRNA were detected in both internal mammary artery and saphenous vein, an effect that was greatly increased by interleukin-1β. These observations show that COX-2 is induced in human saphenous vein and internal mammary artery and suggest that this may occur in humans after coronary artery bypass graft surgery. The induction of COX-2 and subsequent release of prostacyclin may represent an endogenous defense mechanism against endothelial damage incurred during surgical preparation of these vessels for bypass.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
52 articles.
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