Comparison of microsomal prostaglandin E synthase-1 deletion and COX-2 inhibition in acute cardiac ischemia in mice.
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 30min later the left coronary artery was surgically occluded. At 24h, 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 24h 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.
Wu
Dongmei
D
Department of Research, Division of Neonatology, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, FL 33140, USA. dwu@msmc.com
Mennerich
Detlev
D
Arndt
Kirsten
K
Sugiyama
Kenji
K
Ozaki
Naoko
N
Schwarz
Karoline
K
Wei
Jianqin
J
Wu
Heng
H
Bishopric
Nanette H
NH
Doods
Henri
H
D000818:Animals; D054059:Coronary Occlusion / Q000150:complications; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D019746:Intramolecular Oxidoreductases / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse