Post-myocardial infarct p27 fusion protein intravenous delivery averts adverse remodelling and improves heart function and survival in rodents
Bibliographic record
Abstract
AIMS: P27Kip1 (p27) blocks cell proliferation through the inhibition of cyclin-dependent kinase 2 (cdk-2). Despite robust expression in the heart, little is known about the regulation and function of p27 in this terminally differentiated tissue. Previously, we demonstrated that p27 exerts anti-apoptotic and growth-inhibitory effects through interaction with casein kinase 2 (ck2) in neonatal rat cardiomyocytes. Here, we test the hypothesis that delivery of a transactivator of transcription (TAT)-p27 fusion protein (TAT.p27) will improve cardiac function and survival in a rat model of myocardial infarction (MI). METHODS AND RESULTS: Fisher rats underwent permanent left anterior descending ligation-induced MI followed by iv injection of TAT.p27 or TAT.LacZ (20 mg/kg) on Days 1 and 7 post-MI. Delivery of TAT.p27 was evaluated by western blot (WB) and immunofluorescence microscopy. Heart function was assessed by echocardiography and pressure-volume catheter. Apoptosis, hypertrophy, and fibrosis were detected by histochemistry and morphometry. WB confirmed gradual reduction in endogenous cardiac p27 levels following MI, with immunohistochemistry demonstrating successful delivery of TAT.p27 to the heart. At 48 h post-MI, cardiac apoptosis was decreased in rats treated with TAT.p27 when compared with saline- and TAT.LacZ-treated controls. At 28 days post-MI, rats treated with TAT.p27 manifested less cardiomyocyte hypertrophy and fibrosis, less diminished cardiac function, and greater survival. Additionally, p27KO mice undergoing experimental MI suffered an early increase in apoptosis with a larger infarct size and markedly reduced survival when compared with wild-type (WT) controls. CONCLUSION: These gain- and loss-of-function studies reveal a critical role for p27 in cardiac remodelling post-MI.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 teacher head, 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".