Abstract 8299: Loss of Apelin Exacerbates Post-Myocardial Infarction Remodeling and Myocardial Ischemia-Reperfusion Injury
Bibliographic record
Abstract
Objectives: Apelin (APLN), the endogenous peptide ligand of the APJ receptor, improves heart function in patients with heart failure and apelin peptides mediate positive inotropic effects and vasodilation. We hypothesize that there is an exacerbated myocardial ischemic injury in APLN knockout (KO) mice compared to littermate WT. Methods: Male WT (C57Bl/6) and APLN knockout mice were subjected to myocardial infarction (MI) using the LAD ligation technique and mortality and heart function were monitored. Langendorff perfused ex vivo hearts from WT and APLN KO mice were subjected to 30 min global ischemia followed by 40 min reperfusion. Results: LAD ligation in APLN KO mice resulted in greater mortality based on Kaplan-Meir survival analysis (76% vs 48%; p<0.01) at 1 week post-MI. Echocardiography showed greater reduction in ejection fraction in APLN KO mice (18.1±3.5 vs 29.3±3.1%; p<0.05) with greater LV dilation (LV end-diastolic volume=196±14.2 vs 161±13.1 μ L; p<0.05; n=8) at 1 week post-MI. In response to global ischemia-reperfusion (I/R) injury, functional recovery was significantly decreased in APLN KO hearts with LV developed pressure=19.5±2.8 vs 33.8±4.1 mmHg (WT; p<0.05; n=5) at the end of 40 min of reperfusion with significant lowering of the dP/dtmax=1289±65 mmHg/s (WT) versus 610±65 mmHg/s (APLN KO; p<0.05) and dP/dtmin=-657±34 mmHg/s (WT) versus -329±25 mmHg/s (APLN KO; p<0.05) and the rate-pressure product averaging 9975±253 bpm*mmHg (WT) versus 4208±212 bpm*mmHg (APLN KO; p<0.05). Creatine kinase in the coronary perfusate showed a greater increase in APLN KO compared to WT (102.7±17.7 vs 57.5±8.9 U/L; p<0.05) mice in response to I/R injury. Western blot analysis showed reduced phosphorylation of Akt, GSK3β and ERK1/2 in the ischemic-reperfused APLN KO hearts compared with WT hearts. Conclusions: Loss of apelin increases MI-induced mortality, exacerbates post-MI adverse modeling and enhances the susceptibility to I/R injury. Enhancing apelin function may represent a novel therapy for minimizing the myocardial damage in patients with heart disease.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".