D‐4F attenuates calcineurin‐induced cardiac hypertrophy and heart failure
Bibliographic record
Abstract
D‐4F, an apolipoprotein A‐I mimetic, has been shown to improve vascular function in atherosclerosis, diabetes and a variety of inflammatory diseases. However, the potential benefits of D‐4F in cardiac hypertrophy remain unknown. Calcineurin is a calcium‐sensitive type IIB phosphatase, which has been demonstrated to play a role in human heart hypertrophy. Transgenic Calcineurin A (CnA‐TG) mouse is an established murine model of cardiac hypertrophy and heart failure. Here, we investigate whether D‐4F attenuates cardiac hypertrophy and heart failure in CnA‐TG mice. CnA‐TG and wild type mice, immediately after weaning were treated with PBS or D‐4F (1 or 3 mg/kg/day) for 8 weeks. D‐4F dose‐dependently reduced ventricular mass to body weight ratios, cardiomyocyte cell size as well as interstitial fibrosis. Echocardiography revealed that D‐4F significantly prevented left ventricular wall thickness, elevated mitral E/A ratios, decreased E wave deceleration times and cardiac arrhythmias in CnA‐TG mice. Additionally, real‐time PCR shows that D‐4F decreased expression of ANP, β‐MHC; increased expression of sarcoplasmic reticulum Ca 2+ ATPase and c‐fos. Cardiac hemodynamics, plasma lipids and lipoprotein levels were essentially unchanged among the groups. In conclusion, D‐4F effectively reduces cardiac hypertrophy to protect the hearts of CnA‐TG mice from programmed failure.
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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 | 0.001 | 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) | 0.001 | 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".