Induction of cyclooxygenase-2 in human saphenous vein and internal mammary artery.
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-1 beta. COX-2 metabolites, measured by radioimmunoassay, were released by both the internal mammary artery and saphenous vein in the following rank order: prostaglandin E2 > or = prostacyclin thromboxane A2. Inclusion of interleukin-1 beta 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-1 beta. 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.
Bishop-Bailey
D
D
Department of Applied Pharmacology, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, UK.
Pepper
J R
JR
Haddad
E B
EB
Newton
R
R
Larkin
S W
SW
Mitchell
J A
JA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000368:Aged; D015152:Blotting, Northern; D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D008875:Middle Aged; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism*
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases