Growth Suppression of Human Coronary Vascular Smooth Muscle Cells by Gene Transfer of the Transcription Factor E2F-1
Bibliographic record
Abstract
BACKGROUND: The transcription factor E2F-1 promotes S-phase entry and death in transformed cells and primary cardiomyocytes. We tested the hypothesis that overexpression of E2F-1 forces growth-arrested human coronary vascular smooth muscle cells (VSMCs) to enter the S phase, undergo apoptosis, and thereby regulate VSMC growth. METHODS AND RESULTS: Early-passage (</=5 passages) coronary VSMCs were transduced at an MOI of 100 with a recombinant adenovirus encoding human E2F-1. E2F-1 expression was observed by immunohistochemistry as early as 6 to 8 hours after exposure of the VSMCs to Ad.E2F-1 but not to the control vector Ad.RR. When cells were kept in growth-arrest medium, 40% of Ad.E2F-1-treated VSMCs entered the S phase by 96 hours, whereas the percentage remained <5% in Ad.RR-treated cells. Transition to the S phase in the E2F-1-transduced VSMCs was followed by apoptosis, as reflected by chromatin condensation, membrane blebbing, cell detachment, and loss of mitochondrial membrane integrity. E2F-1 overexpression resulted in positive dUTP nick end-labeling mediated by terminal deoxynucleotidyl transferase, associated with a robust increase in caspase 3-like activity. Four days after infection with Ad.E2F-1, the fraction of hypodiploid VSMCs in subG(1) increased to 75%. At 7 days, gene transfer of E2F-1 had completely suppressed the growth of VSMCs, whereas the number of Ad.RR-infected cells had increased >8 times. CONCLUSIONS: Overexpression of the transcription factor E2F-1 regulates growth of human coronary VSMCs by forcing the cells to enter the S phase and then to die. Cell death appears to involve caspase 3-like activity, which, in the VSMCs, is markedly increased by overexpression of E2F-1.
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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 | 0.000 | 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) | 0.000 | 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".