Abstract P278: Fibroblast Growth Factor 21 Mediated Protection of Ischemic Myocardium
Bibliographic record
Abstract
Myocardial ischemia is a prevalent disorder causing heart failure. As cardiomyocyte death is the principal cause of cardiac functional deficits, a recognized treatment is to minimize cardiomyocyte death post myocardial ischemia. While extensive investigations have been conducted, few effective cardioprotective agents have been developed for clinical applications. The goal of this investigation is to test and establish a cardioprotective agent based on fibroblast growth factor 21 (FGF21), a secretory protein participating in innate cardioprotective responses. In myocardial ischemia induced by LAD coronary artery ligation in the mouse, hepatocytes upregulated FGF21 mRNA by 11 folds at 12 hrs, followed by an increase in the FGF21 protein level in hepatocytes and the serum. Administration of recombinant FGF21 to mice immediately post MI (50 ng/gm, IV, twice/day for 3 days) resulted in a significant reduction in the fraction of myocardial infarction (MI) with reference to the LV wall volume below the LAD ligation (38+/−5 and 21+/−4%, n=7, vs. albumin administration 51+/−8 and 31+/−5%, n=6, at day 1 and 10, respectively, p<0.05 for both times) in association with improved LV dp/dt. In FGF21 overexpressing mice, the volume fraction of MI (36+/−6%, n=6) was significantly lower than that in wildtype mice (48+/−6%, n=5, p<0.05) at day 1 post MI. Furthermore, FGF21 administration to normal mice induced phosphorylation of FGFR1, PI3K, Akt, and BAD in cardiomyocytes within 10 – 30 min. These molecules were also phosphorylated in cardiomyocytes within 1 day post MI. Injection of siRNA specific to FGFR1, PI3K, or Akt to the LV anterior wall at 6 locations about 2 mm apart (diffusion range of FITC-siRNA tested by fluorescence microscopy) 3 days prior to MI resulted in a reduction in the protein level of FGFR1, PI3K, or Akt by 65+/−9, 71+/−11, or 68+/−12%, respectively (n=3), within the region of siRNA injection at 1 day post MI in association with a reduction in BAD phosphorylation and an increase in the fraction of MI by 9+/−3, 8+/−2, or 11+/−3%, respectively (n=3). These observations suggested that FGF21 contributed to myocardial protection possibly via the FGFR1-PI3K-Akt-BAD signaling mechanisms and recombinant FGF21 may be potentially used as a cardioprotective agent.
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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 | 0.001 |
| 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".