Cardiomyocyte apoptosis contributes to pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated mice
Bibliographic record
Abstract
Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunctions, electrophysiological changes and macroscopic structural changes. However, the underlying mechanisms of this syndrome remain unclear. A possible role of myocardial apoptosis in the pathogenesis has not been previously examined. We hypothesized that dysregulation of apoptotic signalling participates in cardiac dysfunction in the cirrhotic heart. Therefore, we evaluated apoptotic pathways in the hearts of mice with chronic BDL (bile duct ligation). A cirrhotic cardiomyopathy model was induced by BDL in mice. Left ventricular geometry and volumes were evaluated by MRI. Intrinsic and extrinsic apoptotic pathways were evaluated by immunohistochemical staining and Western blot analysis. Fas-mediated apoptosis was inhibited by in vivo administration of an anti-FasL (Fas ligand) monoclonal antibody, and subsequently cardiac contractility was measured in isolated cardiomyocytes. BDL-mice showed significantly more PARP [poly(ADP-ribose) polymerase] staining than sham controls (18.2±11.4 compared with 6.7±5.3; P<0.05). Fas protein expression and PARP cleavage were activated, whereas FLIP (Fas-associated death domain-like interleukin 1β-converting enzyme-inhibitory protein) was decreased compared with sham controls. The Bcl-2/Bax ratio was increased in BDL-mice compared with sham controls. Anti-FasL monoclonal antibody injection in BDL-mice improved systolic and diastolic dysfunctions in cardiomyocytes, but had no effect in sham controls. A net pro-apoptotic balance exists in BDL hearts, mainly mediated by activation of the extrinsic pathway, and abrogation of apoptosis improved contractility. These results suggest that apoptosis contributes to depressed cardiac contractility in a murine model of cirrhotic cardiomyopathy.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".