Cyclooxygenase-2 Induction in Congestive Heart Failure

Cyclooxygenase-2, like the other member of the COX family, COX-1, is a bifunctional enzyme that catalyzes the conversion of arachidonic acid to PGG2 via COX activity and PGG2 to PGH2 via peroxidase activity. PGH2 is the precursor for PGs, prostacyclin, and TXA2. Hence, COX-2 occupies a central position in the biosynthesis of proinflammatory PGE2 and vasoactive prostacyclin and TXA2. COX-2 shares with COX-1 most of its catalytic and structural properties. The crystallographic structure of COX-2 reveals a branched substrate channel, as contrasted to a nonbranched, more rigid COX-1 channel structure.1 2 This difference in substrate channel structure forms the basis for selective inhibition of COX-2 by newly developed compounds containing a side chain that snugly fits the substrate channel of COX-2 but not COX-1.3 COX-2 is encoded by a gene ≈8 kb in size located on the long arm of chromosome 1 (q25.2–q25.3).4 5 The COX-1 gene, on the other hand, is ≈22 kb and is located on chromosome arm 9q32–q33.3.5 …