In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. 23 ( 2012-06-12), p. 2904-2913
Abstract:
Microsomal prostaglandin E 2 synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E 2 biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges −/− mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges +/+ mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow–derived leukocytes in the recovery of LV function after coronary ligation. Methods and Results— Cardiac structure and function in Ptges +/+ mice with Ptges +/+ bone marrow ( BM +/+ ) and Ptges +/+ mice with Ptges −/− BM ( BM −/− ) were assessed by morphometric analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic enzyme gene expression were measured by liquid chromatography–tandem mass spectrometry and real-time polymerase chain reaction, immunoblotting, immunohistochemistry, and immunofluorescence microscopy, respectively. After myocardial infarction, BM −/− mice had more LV dilation, worse LV systolic and diastolic function, higher LV end-diastolic pressure, more cardiomyocyte hypertrophy, and higher mortality but similar infarct size and pulmonary edema compared with BM +/+ mice. BM −/− mice also had higher levels of COX-1 protein and more leukocytes in the infarct, but not the viable LV, than BM +/+ mice. Levels of prostaglandin E 2 were higher in the infarct and viable myocardium of BM −/− mice than in BM +/+ mice. Conclusions— Lack of mPGES-1 in bone marrow–derived leukocytes negatively regulates COX-1 expression, prostaglandin E 2 biosynthesis, and inflammation in the infarct and leads to impaired LV function, adverse LV remodeling, and decreased survival after acute myocardial infarction.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/CIRCULATIONAHA.112.099754
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2012
detail.hit.zdb_id:
1466401-X
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