Induction of Cyclo-Oxygenase in Human Vessels in vitro

Abstract

Cyclo-oxygenase (COX) converts free arachidonic acid to prostaglandin (PG)H₂, the precursor to a group of lipid mediators including prostacyclin (PGI₂), PGE₂, and thromboxane (TX) A₂. The predominant COX metabolite released from vessels is PGI₂, which is a vasodilator, and an inhibitor of cellular proliferation, platelet adhesion and activation, and cholesterol metabolism (see Willis et al., 1986; Hajjar and Pomerantz, 1992). COX is now known to exist in at least 2 different isoforms; a constitutively expressed COX-1, and a cytokine inducible COX-2 (see Mitchell et al., 1995). Within vessels COX-1 is normally the dominant isoform, and is concentrated mainly in the endothelial cell layer. The underlying vascular smooth muscle has lower COX activity, but is a rich source of PGI₂ synthetase. In animal models, COX-2 is induced in the vascular smooth muscle layer after mechanical damage to the vessel (Rimarchin et al., 1994). However, the expression of COX-2 in human vessels has not been demonstrated.