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 24 h, 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.