The cytoprotective impact of yes-associated protein 1 after ischemia-reperfusion injury in AC16 human cardiomyocytes
Bibliographic record
Abstract
The Hippo-signaling pathway is a mechanism implicated in cardiomyocyte cytoprotection and regeneration after a myocardial infarction. Yes-associated protein 1, the main effector protein of this pathway, acts as a co-transcriptional activator to promote cardiomyocyte proliferation and survival. However, the biological mechanisms by which yes-associated protein 1 protects the heart post-MI are currently unknown. Here, we propose that yes-associated protein 1 plays a critical role in cardiomyocyte cytoprotection after simulated ischemia-reperfusion injury. AC16 human cardiomyocytes were infected with lentiviral plasmids containing normal human yes-associated protein 1 and a constitutively active form of YAP, YAP1S127A. Cells were exposed to ischemia-reperfusion injury using a hypoxic chamber. Hippo-signaling characterization after ischemia-reperfusion injury was performed via Western blotting and reverse transcriptase polymerase chain reaction. Cell viability, apoptosis, and cellular hypertrophy were assessed as a measure of cytoprotection. The GSK3β inhibitor CHIR99021 was used to investigate cross-talk between Hippo and Wnt-signaling and their role in cytoprotection after ischemia-reperfusion-injury. Ischemia-reperfusion injury resulted in significant decreased expression of the non-phosphorylated Hippo signaling kinases MST1 and LATS1, along with decreased expression of YAP/TAZ. Overexpression of yes-associated protein 1 improved cellular viability, while reducing hypertrophy and apoptosis via the ATM/ATR DNA damage response pathway. Activation of β-catenin in YAP-infected cardiomyocytes synergistically reduced cellular hypertrophy after ischemia-reperfusion-injury. Our findings indicate that yes-associated protein 1 is cytoprotective in AC16 human cardiomyocytes after ischemia-reperfusion injury, which may be mediated by co-activation of the canonical Wnt/β-catenin pathway. Thus, activation of yes-associated protein 1 may be a novel therapeutic to repair the infarcted myocardium. Impact statement Genetically engineering the cells of the heart after myocardial infarction to display a more regenerative phenotype is a promising therapy for heart failure patients. Here, we support a regenerative role for yes-associated protein 1, the main effector protein of the Hippo signaling pathway, in AC16 human cardiomyocytes as a potential therapeutic gene target for cardiac repair after myocardial infarction.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".