Non-angiogenic FGF-2 protects the ischemic heart from injury, in the presence or absence of reperfusion
Bibliographic record
Abstract
OBJECTIVE: Fibroblast growth factor-2 (FGF-2), given during ischemia or during reperfusion of the ischemic heart is cardioprotective, but its mitogenic activity may limit possible clinical applications. We have tested the cardioprotective potential of a non-mitogenic FGF-2 mutant (S117A) that no longer activates casein kinase 2 (CK2) in both acute and long-term studies. METHODS AND RESULTS: To test effects during reperfusion, the ex vivo rat heart, subjected to 30 min of global ischemia and 60 min of reperfusion was used. S117A FGF-2 administered during reperfusion protected against myocardial contractile dysfunction, activated protein kinase C and decreased the release of cytochrome C in the cytosol. To study effects on ischemic myocytes in the absence of reperfusion, myocardial infarction (MI) was induced in the rat model by irreversible left coronary ligation. S117A-, wild type (wt)-FGF-2 or saline, were administered by intramyocardial injection into the ischemic ventricular wall. One day later, infarct size (assessed by tetrazolium staining), and plasma cardiac troponin T levels (assessed by Western blotting) were significantly decreased in the S117A FGF-2-, compared to the saline-treated group. Systolic pressure, rates of contraction and relaxation and developed pressure, assessed in the Langendorff mode, were significantly improved in the S117-FGF-2 group. Improved ejection fraction and fractional shortening in the S117A-treated group were maintained up to, but not beyond, 7 days post-MI. In comparison, improvements were maintained in the wt-FGF-2-treated group at least up to 6 weeks post-MI. At 6 weeks post-MI, small vessel density (assessed by immunofluorescence-based detection) in the scar bordering viable myocardium was similar between S117A-FGF-2- and saline-treated hearts, but significantly increased in the wt-FGF-2-treated group. This was accompanied by increased coronary flow in the wt-, but not S117A-FGF-2-treated hearts, compared to controls. CONCLUSION: The ability of FGF-2, administered during ischemia or during reperfusion, to protect the myocardium acutely from tissue loss and dysfunction is independent of its potential for CK2 activation and angiogenesis. Non-angiogenic S117A-FGF-2 may be considered in therapies aiming for acute prevention of reperfusion-associated pathologies, especially in cases where use of mitogens is counter-indicated.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".