Abstract 162: c-fos Protects the Myocardium from Ischemic Injury and Improves Cardiac Function
Bibliographic record
Abstract
Background: c-fos is an immediate early response gene. c-Fos proteins form heterodimers with Jun family proteins, and the resulting AP-1 complexes regulate transcription by binding to the AP-1 sequence found in many cellular genes. c-fos is activated in cardiomyocytes following myocardial infarction. However, the role of c-fos in regulating cardiomyocyte survival and cardiac function post myocardial infarction (MI) is not known. In the present study, we hypothesized that c-fos protects the myocardium from ischemic injury and improves cardiac function. Methods and Results: The generation of mice with cardiomyocyte specific c-fos −/ − was achieved by crossing the floxed c-fos mice with mice over-expressing Cre recombinase under the control of α-myosin heavy chain. Wild-type (WT) littermates were used as controls. MI was induced by coronary artery ligation. Infarct size, myocardial apoptosis and cardiac function were determined at 2 days post-MI. While area at risk was similar between the 2 groups, infarct size was significantly increased in c-fos −/ − compared to WT mice (58 ± 4% vs. 44 ± 3%, P< 0.05). Myocardial caspase-3 activity and cytosolic DNA fragments in the peri-infarct region were significantly increased while Bcl-2/Bax protein ratio was significantly decreased in c-fos −/− mice ( P< 0.05). LV pressure volume relationship was assessed in vivo using a Millar pressure conductance catheter. LV end-systolic elastance ( E es ) and +d P /dt max were significantly decreased in c-fos −/− compared to WT mice (1.7 ± 0.4 vs. 5.1 ± 1.0 mmHg/μL; 4776 ± 567 vs. 7006 ± 319 mmHg/s, P< 0.01). Conclusions: Deficiency in c-fos increases infarct size and myocardial apoptosis leading to impaired cardiac function post-MI. Our results suggest that c-fos protects the myocardium from ischemic injury and improves cardiac function.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.014 | 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".