RT Journal Article
SR Electronic
T1 Myeloid cell mPges-1 depletion attenuates mortality without affecting remodeling after acute myocardial infarction in mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.118.256057
DO 10.1124/jpet.118.256057
A1 Lihong Chen
A1 Guangrui Yang
A1 Tingting Jiang
A1 Soon Yew Tang
A1 Tao Wang
A1 Qing Wan
A1 Miao Wang
A1 Garret A FitzGerald
YR 2019
UL http://jpet.aspetjournals.org/content/early/2019/04/16/jpet.118.256057.abstract
AB Selective deletion 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 3, 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. Left ventricular systolic (reflected by ejection fraction, fractional shortness end systolic volume and +dP/dt) and diastolic function (reflected by end diastolic volume, -dP/dt and Tau), cardiac hypertrophy (reflected by LV dimensions) and staining for fibrosis did not differ between the groups. In conclusion, we find that 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.SIGNIFICANCE STATEMENT None