Circulation. 1998;98:95-96
(Circulation. 1998;98:95-96.)
© 1998 American Heart Association, Inc.
Cyclooxygenase-2 Induction in Congestive Heart Failure
Friend or Foe?
Kenneth K. Wu, MD, PhD
From the Vascular Biology Research Center and Division of Hematology,
Department of Internal Medicine, University of Texas–Houston Medical
School.
Correspondence to Kenneth K. Wu, MD, PhD, University of Texas–Houston Medical School, 6431 Fannin, MSB 5.016, Houston, TX 77030. E-mail kkwu@heart.med.uth.tmc.edu
Key Words: Editorials • prostaglandins • myocytes • NF-kappa B
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 6 In contrast to
COX-1, which is constitutively expressed in most tissues, COX-2
expression is induced in inflammatory cells by a variety of agents,
including cytokines, mitogenic factors, PGs, and
hypoxia.7 These agents induce COX-2
transcription by involving different regulatory elements and putative
binding sites on the 5'-flanking untranslated region of the
COX-2 gene.4 It has been shown in
murine 3T3 cells that COX-2 induction by v-src,
platelet-derived growth factor, or serum is mediated by the cAMP
response element at -59 to -53.8 9 COX-2
induction in bovine endothelial . . . [Full Text of this Article]
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