Role for DNA repair signaling in coronary artery stenosis (1071.9)
Bibliographic record
Abstract
Coronary artery stenosis is a vascular disease characterized by sustained inflammation and oxidative stress, leading to DNA damage. Despite these detrimental conditions, coronary artery smooth muscle cells (CoASMC) show increased proliferation and suppressed apoptosis leading to luminal narrowing. PARP‐1 is a critical enzyme acting as DNA damage sensor by promoting either DNA repair or apoptosis depending on the amount of damage. Recent studies demonstrated the implication of the glycogen synthase 3 (GSK3) enzyme, which when inhibited, favors DNA repair (promoting cell survival and proliferation) and resistance to apoptosis (by promoting mitochondrial hyperpolarization). Thus, we hypothesized that increased DNA damage in coronary artery of patients with stenosis promotes PARP‐1 activation and GSK3 inhibition. In freshly isolated human CoASMC issued from control or stenosed arteries, we measured DNA damage, PARP‐1 expression and phosphorylated GSK3 protein levels. We demonstrated that CoASMC from stenosed arteries exhibit increased DNA damage, enhanced PARP‐1 expression and GSK3 inhibition. These cells also present mitochondrial membrane hyperpolarization and consequently show increased proliferation and suppressed apoptosis. Our study suggests an important role of DNA damage signaling and metabolism dysfunction in coronary stenosis and opens the door to new avenues of investigation and treatment. Grant Funding Source : Supported by CIHR grants
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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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".