Over-expression of mitochondria-targeted calpain-1 induces dilated heart failure in transgenic mice: an important role of mitochondrial reactive oxygen species
Bibliographic record
Abstract
Ting Cao*, Dong Zheng, Lulu Zhang, Rui Ni, Tianqing Peng Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China. Lawson Health Research Institute, Departments of Medicine and Pathology and Laboratory Medicine, Western University, London, Ontario, Canada Background: Calpain-1 has been shown to increase in mitochondria of the heart under certain pathological conditions. Increased calpain-1 in mitochondria is associated with myocardial dysfunction. Aims: This study was to investigate forced up-regulation of calpain-1 in mitochondria induces myocardial injury and heart failure. Methods and Results: A novel line of transgenic mice over-expressing cardiomyocyte-specific and mitochondria-targeted calpain-1 was generated. Over-expression of mitochondria-targeted calpain-1 increased mitochondrial superoxide generation in hearts and induced cardiac hypertrophy, fibrosis and ventricular chamber dilation, leading to myocardial dysfunction and early death in transgenic mice. These effects of mitochondrial calpain-1 up-regulation were attenuated by administration of mitochondria-targeted antioxidant mito-TEMPO. Increased mitochondrial calpain-1 also correlated with mitochondrial dysfunction in transgenic mouse hearts. Conclusions: Mitochondrial calpain-1 induces myocardial injury and dysfunction likely by promoting mitochondrial superoxide generation. Thus, mitochondrial calpain-1 may represent a novel mechanism underlying heart 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) | 0.000 | 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".