Abstract 4301: Chimeric Mice Lacking Microsomal Prostaglandin E <sub>2</sub> Synthase-1 (mPGES) In Bone Marrow Develop Adverse Left Ventricular Remodelling After Myocardial Infarction
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".