title: The effects of microsomal prostaglandin E synthase-1 deletion in acute cardiac ischemia in mice.
abstract: 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.
authors.affiliation: Department of Research, Division of Neonatology, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, FL 33140, USA. dwu@msmc.com
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.forename: Detlev
authors.initials: D
authors.lastname: Mennerich
authors.forename: Kirsten
authors.initials: K
authors.lastname: Arndt
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Naoko
authors.initials: N
authors.lastname: Ozaki
authors.forename: Karoline
authors.initials: K
authors.lastname: Schwarz
authors.forename: Jianqin
authors.initials: J
authors.lastname: Wei
authors.forename: Heng
authors.initials: H
authors.lastname: Wu
authors.forename: Nanette H
authors.initials: NH
authors.lastname: Bishopric
authors.forename: Henri
authors.initials: H
authors.lastname: Doods
mesh_terms: 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
chemical_list: 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