The effects of microsomal prostaglandin E synthase-1 deletion in acute cardiac ischemia in mice.
The goal of the present study was to assess how genetic loss of microsomal prostaglandin E(2) synthase-1 (mPGES-1) affects acute cardiac ischemic damage after coronary occlusion in mice. Wild type (WT), heterozygous (mPGES-1(+/-)), and homozygous (mPGES-1(-/-)) knockout mice were subjected to left coronary artery occlusion. At 24h, myocardial infarct (MI) volume was measured histologically. Post-MI survival, plasma levels of creatine phosphokinase (CPK) and cardiac troponin-I, together with MI size, were similar in WT, mPGES-1(+/-) and mPGES-1(-/-) mice. In contrast, post-MI survival was reduced in mPGES-1(-/-) mice pretreated with I prostanoid receptor (IP) antagonist (12/16) compared with vehicle-treated controls (13/13 mPGES-1(-/-)) together with increased CPK and cardiac troponin-I release. The deletion of mPGES-1 in mice results in increased prostacyclin I(2) (PGI(2)) formation and marginal effects on the circulatory prostaglandin E(2) (PGE(2)) level. We conclude that loss of mPGES-1 results in increased PGI(2) formation, and in contrast to inhibition of PGI(2), without worsening acute cardiac ischemic injury.
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; D001593:Benzyl Compounds / Q000494:pharmacology; D003402:Creatine Kinase / Q000097:blood; D011464:Epoprostenol / Q000096:biosynthesis; D007093:Imidazoles / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000097:blood* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology; D000071876:Prostaglandin-E Synthases; D019210:Troponin I / Q000097:blood
C514222:(2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline); D001593:Benzyl Compounds; D007093:Imidazoles; D019210:Troponin I; D011464:Epoprostenol; D003402:Creatine Kinase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse