Differential Induction of Cyclooxygenase-2 in Human Arterial and Venous Smooth Muscle

Role of Endogenous Prostanoids

Correspondence to Jane A. Mitchell, Unit of Critical Care Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. E-mail j.mitchell{at}rbh.nthames.nhs.uk

Abstract—Two isoforms of cyclooxygenase (COX) have been identified: a constitutive isoform (COX-1), found in abundance in platelets and the vascular endothelium, and an "inflammatory" cytokine-inducible isoform (COX-2). Because COX metabolites regulate vascular smooth muscle cell (SMC) function and the interaction between the vessel and circulating components, we have investigated the possibility that COX-2 can be induced in human arterial or venous SMC. Untreated venous or arterial cells contained undetectable levels of COX-1 or COX-2 and released low levels of metabolites. After stimulation with interleukin-1ß, tumor necrosis factor-, interferon-, and bacterial lipopolysaccharide, both venous and arterial SMC expressed COX-2 protein and released increased amounts of prostaglandins. In addition, the induced release of PGE₂ was inhibited by the COX-2–selective inhibitor, L-745,337. When cells were treated with the mixture of cytokines, venous SMC expressed greater amounts of COX-2 protein and released more prostaglandins than arterial SMC. Furthermore, when COX-2 activity was blocked by L-745,337, COX-2 expression in arterial SMC, but not in venous SMC, increased. Thus, this article describes, for the first time, that COX-2 is expressed in greater amounts in venous SMC than in arterial SMC. Moreover, we show that this "differential induction" is due to a negative-feedback pathway for COX-2 expression in arterial SMC but not in venous SMC. The ability of COX-2 activity to limit COX-2 expression in some cells but not others may contribute to the highly developed mechanisms involved in prostanoid release.

Key Words: saphenous vein • internal mammary artery • atherosclerosis • coronary artery bypass grafting

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