Microsomal Prostaglandin E <sub>2</sub> Synthase-1 Deletion Leads to Adverse Left Ventricular Remodeling After Myocardial Infarction
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Bibliographic record
Abstract
BACKGROUND: Pharmacological inhibition of cyclooxygenase-2 increases the risk of myocardial infarction (MI) and stroke. Microsomal prostaglandin (PG) E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, functions downstream from cyclooxygenase-2 in the inducible PGE(2) biosynthetic pathway. We caused acute MI in Ptges(+/+) and Ptges(-/-) mice to define the role of mPGES-1 in cardiac ischemic injury. METHODS AND RESULTS: Twenty-eight days after MI, Ptges(-/-) mice develop more left ventricular (LV) dilation, have worse LV systolic and diastolic function, and have higher LV end-diastolic pressure than Ptges(+/+) mice but have similar pulmonary wet-to-dry weight ratios, cardiac mass, infarct size, and mortality. The length-to-width ratio of individual cardiomyocytes is significantly greater in Ptges(-/-) than Ptges(+/+) mice after MI, a finding consistent with eccentric cardiomyocyte hypertrophy in Ptges(-/-) mice. Expression of atrial natriuretic peptide, brain natriuretic peptide, and alpha- and beta-myosin heavy chain, markers of ventricular hypertrophy, is higher in the LV of Ptges(-/-) than Ptges(+/+) mice after MI. Ptges(+/+) mice express cyclooxygenase-2 and mPGES-1 protein in inflammatory cells adjacent to the infarct after MI but do not express these proteins in cardiomyocytes. Ptges(-/-) mice express cyclooxygenase-2 in inflammatory cells adjacent to the infarct and do not express mPGES-1 in any cells in the heart. Levels of PGE(2) but not PGD(2), thromboxane A(2), PGI(2), or PGF(2alpha) are higher in the infarct and LV remote from the infarct after MI in Ptges(+/+) than Ptges(-/-) mice. CONCLUSIONS: In Ptges(+/+) mice, mPGES-1 in inflammatory cells catalyzes PGE(2) biosynthesis in the LV after MI. Deletion of mPGES-1 leads to eccentric cardiac myocyte hypertrophy, LV dilation, and impaired LV contractile function after acute MI.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it