Role of neuronal nitric oxide synthase in heart failure post myocardial infarction in mice
Bibliographic record
Abstract
Objectives Anoxia and reoxygenation (A/R) increases reactive oxygen species and induces cardiomyocyte apoptosis. However, the role of superoxide (O 2 − ) produced by NADH oxidase in this process is not clear. We hypothesized that activation of gp91 phox ‐containing NADH oxidase protects cardiomyocytes from apoptosis during A/R. Methods and Results Experiments were performed in primary cultured neonatal cardiomyocytes and isolated hearts from wild‐type (WT) and gp91 phox−/− mice. Cardiomyocytes were challenged with 1 hr of anoxia followed by 30 min of reoxygenation. Apoptosis was determined by caspase‐3 activity and TUNEL staining. In WT cardiomyocytes, A/R increased O 2 − production with no changes in mRNA or protein levels of NADH oxidase membrane (gp91 phox , p22 phox ) or cytoplasmic subunit (p47 phox ). After A/R, O 2 − formation was significantly decreased while caspase‐3 activity and TUNEL‐positive cells were significantly increased in gp91 phox−/− compared to WT cardiomyocytes ( P <0.05). Furthermore, A/R‐induced cytochrome c release from mitochondria was enhanced in gp91 phox−/− cardiomyocytes, which was accompanied by significant lower Bcl‐2 protein levels. In isolated hearts subjected to 45 min of ischemia followed by 90 min of reperfusion (I/R), caspase‐3 activity was significantly increased, while cardiac contractility and heart work were significantly decreased in gp91 phox−/− compared to WT mice ( P <0.05). Conclusions Our data demonstrate deficiency in gp91 phox results in increased cardiomyocyte apoptosis and decreased cardiac function, suggesting a protective role of gp91 phox ‐containing NADH oxidase in myocardial I/R.
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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".