Abstract 4143866: The Effect of S100A6 Gene Therapy on Cardiac Function in a Rat Model of Ischemic Cardiomyopathy
Bibliographic record
Abstract
Background: S100A6 is a small calcium-binding protein that is important in managing calcium storage and myocyte contractility. This protein has a low basal cardiac expression and is upregulated following Myocardial Infarction (MI). Previous experiments have demonstrated that S100A6 gene transfer improves left ventricular function after acute ischemia/reperfusion injury. Hypothesis: Delivery of S100A6 by Ultrasound-Targeted Microbubble Destruction (UTMD) after established MI model results in improved left ventricular function and prevention of adverse ventricular remodeling. Aim: Assess the impact of UTMD delivery of S100A6 on cardiac function following experimental MI. Methods: MI was induced through permanent left anterior descending (LAD) coronary artery ligation in 8-week-Spragues Dawley (SD) male rats on day 0. On day 28, by using UTMD methods, we delivered microbubbles (1×109) coupled with either 200 μg of human S100A6 mini-circle DNA or empty minicircles to the left ventricle (LV), while control animals received no therapy. The three groups were monitored weekly for four weeks post-gene delivery using serial echocardiography to follow LV function, followed by tissue collection from various regions of the myocardium. Results: At day 28 post-MI, all groups showed reduced LV ejection fraction (LVEF) and fractional shortening (FS), with LVEF and FS values of 39.47±1.49% and 19.75±2.38%, respectively. Meanwhile, healthy animals showed LVEF and FS values of (63.75±2.38% and 36.20±1.29% (p<0.001). Four weeks after the UTMD delivery of the S100A6, LVEF increased to 51.14±3.7% and FS increased to 29.66±3.2% (p<0.05). In contrast, the empty minicircle and control groups showed no significant improvement (38.35±2.6% and 20.66±5.2%, p<0.05). The S100A6-treated group at 28 days post-treatment showed a 2.7±1.2-fold increase in the expression level of S100A6 in the border zones. Interestingly, the peri-infarct zone of S100A6-treated myocardium also had a lower expression level of the hypertrophic marker, β-MHC (0.77±0.7-fold), as compared to those of the control groups (2.48±1.63-fold). S100A6 transfection reduced infarct size (24.75±3.3%); vs control (36±4.58%), p<0.05 and decreased collagen content in viable myocardium compared to the control and empty minicircle group, p<0.01. Conclusion: S100A6 overexpression in the peri-infarct zone decreased both hypertrophy and fibrosis and was beneficial to the preservation of cardiac function in a model of chronic MI.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".