Ac-SDKP and eplerenone confer additive cardioprotection against angiotensin II-induced cardiac injury in C57BL/6J mice
Bibliographic record
Abstract
Eplerenone, a mineralocorticoid receptor antagonist, is an anti-hypertensive and cardioprotective drug. We showed that N-Acetyl-Seryl-Aspartyl-Proline (Ac-SDKP) exerts beneficial effects on the heart. Whether Ac-SDKP provides additional cardioprotective effects if combined with eplerenone in angiotensin II (Ang II)-induced hypertension remains unknown. Male C57BL/6J mice were treated with either sham, Ang II (2.9 mg/kg/day, s.c.), Ang II + Ac-SDKP (1.6 mg/kg/day, s.c.), Ang II + Eplerenone (150 mg/kg/day in mouse chow), or Ang II + Ac-SDKP + Eplerenone. Treatment lasted for eight weeks. Systolic blood pressure (SBP) measurements were taken weekly. Echocardiography (Echo) and magnetic resonance imaging (MRI) were performed at the end of the experiment. SBP was increased in all mice with Ang II and was not affected by any treatment. Posterior wall thickness (PWT) and left ventricular (LV) mass were increased in Ang II-treated groups. LV mass was not significantly affected by treatment, but PWT was reduced by both monotherapies and showed the greatest reduction with combined Ac-SDKP and eplerenone. Ejection fraction (EF) decreased in the Ang II group compared to the sham group. EF increased with all treatments (MRI), and there was a further significant increase in EF for mice treated with Ac-SDKP + Eplerenone compared to those receiving a single treatment (Echo). Our data indicate that treatment with Ac-SDKP or Eplerenone improves cardiac function in Ang II-induced hypertension, and supplying Ac-SDKP to Eplerenone provides additive, not synergistic, cardioprotective effects. These beneficial effects were associated with decreased myocardial collagen accumulation, CD68-positive macrophage infiltration, and the expression of CHOP, an endoplasmic reticulum stress mediator. Ac-SDKP could be an effective supplementary treatment alongside Eplerenone for managing hypertension-associated cardiac damage and dysfunction.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 0.001 |
| 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".