Comparison of microsomal prostaglandin E synthase-1 deletion and COX-2 inhibition in acute cardiac ischemia in mice

Dongmei Wu, Detlev Mennerich, Kirsten Arndt, Kenji Sugiyama, Naoko Ozaki, Karoline Schwarz, Jianqin Wei, Heng Wu, Nanette H. Bishopric, Henri Doods

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The aim of the present study was to compare the effects of genetic mPGES-1 loss and COX-2 inhibition on myocardial damage after coronary occlusion. mPGES-1-/- mice and their wild-type littermates were injected with vehicle or COX-2 inhibitor (celecoxib), and 30 min later the left coronary artery was surgically occluded. At 24 h, myocardial infarct (MI) volume was measured histologically. Post-MI survival was reduced in WT mice receiving celecoxib (12/20) compared with vehicle-treated controls (12/12) or the loss of mPGES-1 (13/13) together with increased phosphokinase (CPK) and cardiac troponin-I release. Endogenous mPGES-1 expression was unchanged by ischemia in WT mice and absent in mPGES-1-/- hearts. COX-2 expression was markedly increased at 24 h after MI in WT hearts; this upregulation was largely attenuated in mPGES-1-/- mice. We conclude that loss of mPGES-1 prevents the upregulation of COX-2 after myocardial infarct, and in contrast to inhibition of COX-2, does not increase ischemic myocardial damage.

Original languageEnglish (US)
Pages (from-to)21-25
Number of pages5
JournalProstaglandins and Other Lipid Mediators
Volume90
Issue number1-2
DOIs
StatePublished - Nov 1 2009

Keywords

  • Cyclooxygenase-2
  • Microsomal prostaglandin E synthase-1
  • Myocardial ischemia
  • Prostaglandin E

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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