Relative contributions of correcting the diet and voluntary exercise to myocardial recovery in a two-hit murine model of heart failure with preserved ejection fraction
Bibliographic record
Abstract
Abstract We recently proposed a new two-hit murine model of heart failure with preserved ejection fraction (HFpEF) amenable for both male and female animals. Using this model, we studied cardiac reverse remodelling (RR) after stopping the causing stress (Angiotensin II (AngII) + High-fat diet; MHS) after 28 days, and then introducing voluntary exercise (VE) and feeding the animals with a low-fat diet. We showed this could lead to extensive cardiac left ventricle (LV) RR. Revisiting this HFpEF model, we studied the relative contribution to RR of correcting the diet and/or starting VE after stopping AngII. We also evaluate the extent of myocardial recovery after an extended period (12 weeks instead of four) by exposing the animals to a second MHS. Our observations revealed a sex-specific response. Discontinuing AngII but continuing the HFD blocked RR in females, not males. Removing AngII and correcting either the diet or implementing VE normalized most tested gene markers of LV hypertrophy or extracellular matrix, irrespective of sex. Twelve weeks of recovery was associated with normal LV morphology and function, except for abnormal diastolic echocardiographic parameters. A second MHS after these 12 weeks led to a loss of ejection fraction in males and LV dilatation. The response of females was like that after the first MHS, suggesting a better recovery. The MHS changed markers of myocardial glucose metabolism. Pyruvate dehydrogenase (PDH) activity responsible for pyruvate entry in the mitochondria was reduced after MHS, and this was accompanied by an increase of PDH phosphorylation and pyruvate dehydrogenase kinase 4 content. RR mostly normalized these. Our results suggest sex-specific RR after stopping the MHS and that myocardial anomalies remaining in males make them more sensitive to a second HFpEF-inducing stress.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".