Altered Cardiolipin Metabolism is Associated with Cardiac Mitochondrial Dysfunction in Pulmonary Vascular Remodeled Perinatal Rat Pups
Bibliographic record
Abstract
Abstract Background Pulmonary vascular remodeling (PVR) in utero results in the development of heart failure (HF). The alterations that occur in cardiac lipid and mitochondrial bioenergetics during the development of in utero PVR was unknown. Methods PVR was induced in pups in utero by exposure of pregnant dams to indomethacin and hypoxia. Cardiac lipids, echocardiographic function and cardiomyocyte mitochondrial function were subsequently examined. Results Perinatal rat pups with PVR exhibited elevated left and right cardiac ventricular internal dimensions and reduced ejection fraction and fractional shortening compared to controls. Cardiac myocytes from these pups exhibited increased glycolytic capacity and glycolytic reserve compared to controls. However, respiration with glucose as substrate was unaltered. Fatty acid oxidation and ATP-insensitive respiration were increased in isolated cardiac myocytes from these pups compared to controls indicating mitochondrial dysfunction. Although abundance of mitochondrial respiratory complexes were unaltered, increased trilinoleoyl-lysocardiolipin levels in these pups was observed. A compensatory increase in both cardiolipin (CL) and phosphatidylethanolamine (PE) content were observed due to increased synthesis of these phospholipids. Conclusion Alterations in cardiac cardiolipin and phospholipid metabolism in PVR rat pups is associated with the mitochondrial bioenergetic and cardiac functional defects observed in their hearts. Impact statement - Phospholipid metabolism was examined in pulmonary vascular remodeling in perinatal rat pups. - Pulmonary vascular remodeling was induced in utero by treating pregnant dams with hypoxia and indomethacin at 19-21 days of gestation. - The offspring exhibited altered pulmonary arterial remodeling with subsequent cardiac hypertrophy, ventricular dysfunction, cardiac myocyte mitochondrial dysfunction with altered fatty acid utilization. - In addition, the offspring exhibited elevated cardiolipin, lysocardiolipin and phosphatidylethanolamine content which may potentially contribute to the cardiac mitochondrial dysfunction.
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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) | 0.000 | 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".