Implication of Cyclophilin D and Permeability Transition Pore in Mitochondrial Vulnerability of Compensated Heart Hypertrophy
Bibliographic record
Abstract
The goal of the present study was to investigate the mechanisms involved in the development of vulnerability to permeability transition pore (PTP) opening in the hypertrophied but compensated heart. Hypertrophy was induced by an aorto‐caval fistula (ACF) in WKHA rats. Mitochondria were isolated 12 weeks post‐surgery for measurement of respiratory function, PTP sensitivity to Ca 2+ , ROS production, endogenous matrix Ca 2+ and expression/localization of the PTP regulating protein Cyp‐D. Sensitivity to Ca 2+ ‐induced PTP opening was increased in ACF vs sham in absence of basal respiratory dysfunctions. Total expression of Cyp‐D and the membrane/soluble ratio was superior in the ACF group. Increased membrane binding of Cyp‐D, which is known to facilitate PTP opening, was not reversed by in vitro pre‐incubation with high levels of the PTP inhibitor and Cyp‐D ligand CsA. However, ACF mitochondria also produced more ROS in vitro and displayed increased levels of matrix Ca 2+ , both of which being factors that favor the recruitment of Cyp‐D from the soluble to the membrane fraction. These results suggest that early modifications of key PTP regulators, including an increase in Cyp‐D expression and membrane recruitment, contribute to the development of mitochondrial vulnerability in the hypertrophied heart. Those changes may predispose compensated hypertrophied hearts to further cellular dysfunction, ultimately leading to the activation of cell death typically observed in the transition to heart failure. Funded by CIHR and FRSQ.
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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 | 0.000 |
| 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".