Abstract 14122: Myeloid Cell mPGES-1 Depletion Attenuates Mortality After Myocardial Infarction in Mice
Selective depletion of microsomal PGE2 synthase (mPGES) -1 in myeloid cells retards atherogenesis and suppresses the vascular proliferative response to injury, while it does not predispose to thrombogenesis or hypertension. However, studies using bone marrow transplants from irradiated mice suggest that myeloid cell mPGES-1 facilitates cardiac remodeling and prolongs survival after experimental myocardial infarction (MI). Here we addressed this question using mice lacking mPGES-1 in myeloid cells, particularly macrophages (Mac-mPGES-1 KO), generated by crossing mPGES-1 floxed mice with LysMCre mice, and subjecting them to coronary artery ligation. Cardiac structure and function were assessed by morphometric analysis, echocardiography, and invasive hemodynamics 7 and 28 days after MI. Despite a similar infarct size, in contrast to the prior report, the post-MI survival rate was markedly improved in the Mac-mPGES-1 KO mice compared to WT controls (92.9% vs. 55.6%, p=0.03). Left ventricular systolic (reflected by ejection fraction, fractional shortening, end systolic pressure, and +dP/dt) and diastolic function (reflected by end diastolic pressure, -dP/dt, and Tau), cardiac hypertrophy (reflected by LV dimensions) and staining for fibrosis did not differ between the groups. In conclusion, Cre-loxP mediated deletion of mPGES-1 in myeloid cells has favorable effects on post-MI survival, with no detectable adverse influence on post-MI remodeling. These results add to evidence that targeting macrophage mPGES-1 may represent a safe and efficacious approach to the treatment and prevention of cardiovascular inflammatory disease.
Author Disclosures: L. Chen: None. G. Yang: None. G. FitzGerald: None.
- © 2015 by American Heart Association, Inc.