Abstract 4301: Chimeric Mice Lacking Microsomal Prostaglandin E 2 Synthase-1 (mPGES) In Bone Marrow Develop Adverse Left Ventricular Remodelling After Myocardial Infarction

• Introduction. mPGES functions downstream from COX-2 in the inducible PGE 2 biosynthetic pathway, and can be expressed by cardiac myocytes and inflammatory cells. mPGES gene targeted mice (mPGES −/− ) develop LV dilation and impaired contractile function after MI. The purpose of this study was to determine if mPGES in bone marrow (BM) derived inflammatory cells regulates LV remodelling after MI. Methods. Six week old female mPGES +/+ mice were irradiated with 9.5 Gy and transplanted with BM from male mPGES +/+ or mPGES −/− mice (BM +/+ or BM −/− chimeras, respectively). After 10 weeks, the left coronary artery was ligated. Echocardiography was used to assess LV dimensions and function in vivo . After fixation in situ , LV dimensions and infarct volume was assessed by planimetry. The efficiency of BM transplantation, determined by the ratio of syr to gapdh DNA, measured by real time PCR, was 98%. Results. There was no difference in LV dimensions or function between BM +/+ and BM −/− mice before MI (not shown). Between 7 and 28 days post MI, ejection fraction did not change in BM +/+ mice, but decreased significantly in BM −/− mice (Table ). BM −/− mice also had a higher LV diameter (2.7 ± 0.1 vs. 3.1 ± 0.1 mm, p = 0.0001) and LV volume (14 ± 0.8 vs. 18 ± 1.0 mm 3 , p = 0.025) than BM +/+ mice 28 days after MI. In contrast, there was no difference in the percentage of infarcted LV, heart rate or cardiac output between BM +/+ and BM −/− mice after MI. Survival of BM +/+ vs. BM −/− 28 days after MI was similar (75% vs. 72%, log rank, p = 0.86). Conclusion. mPGES1 in bone marrow cells that localize to the heart after MI is necessary to maintain post infarction LV contractile function, and to prevent adverse LV remodelling. Use of mPGES inhibitors as substitutes for COX-2 inhibitors may be detrimental in patients with coronary artery disease.

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