Post‐Infarct Remodeling in the Myocardium is Regulated by Hippo/YAP Signaling
Bibliographic record
Abstract
BACKGROUND Ventricular remodeling is a complex process involving cell death, inflammation, fibrosis, cardiomyocyte hypertrophy. Recent studies show that Hippo/YAP signaling regulates cardiomyocyte growth and survival following ischemic injury in the myocardium. However, its role in ventricular remodeling is still poorly understood and may hold the potential for therapeutic targeting. In this study, we investigated the expression of Hippo/YAP signaling proteins in the mouse model of acute myocardial infarction. METHODS For acute myocardial infarction (AMI), mice were sedated with ketamine (50mg/kg) and xylazine (5mg/kg), intubated, ventilated, and maintained with 2% isoflurane. Through a left thoracotomy, the left coronary artery was ligated 1 to 2 mm below the border of the left atrial appendage. Animals were sacrificed after 4 weeks post AMI and hearts were harvested and frozen at −80°C. Tissues were homogenized and subjected to western blot analysis. RESULTS Immunoblot analysis of heart tissues show increased expression of β‐MHC, a protein commonly associated with ventricular remodeling and hypertrophy, in 4 week AMI hearts compared to sham. We report a significant increase in Hippo pathway components like Mst1, Mst2, pMob1 and YAP binding protein such as 14‐3‐3 in 4 week AMI hearts compared to sham hearts. On the other hand, YAP expression was reduced in 4 week AMI group compared to control group. CONCLUSION Collectively, our data suggest that the kinase cascade in Hippo/YAP pathway is activated resulting in YAP inactivation, which may contribute to ventricular remodeling following myocardial infarction. Support or Funding Information Natural Sciences and Engineering Research Council of Canada
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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".