Replicative senescence of vascular endothelial cells isolated from coronary patients is worsened by oxidative stress associated with risk factors for cardiovascular disease
Bibliographic record
Abstract
The p53‐p21 pathway can trigger senescence either by telomere shortening (replicative senescence via ATM) or following exposure to oxidative stress and DNA damages (stress‐induced senescence, SIS, via caveolin‐1). Our objective was to determine the main pathway in endothelial cells (EC) from coronary patients exposed to risk factors for cardiovascular diseases (CVD). EC were isolated from human internal mammary artery discarded during CABG (n = 56) and cultured in vitro until senescence. We quantified senescence by cytochemical detection of senescence‐associated b‐galactosidase, telomere length (RFL) by Southern blotting, gene expression of p53, p21, ATM and caveolin‐1 (Cav‐1) by qPCR and levels of lipid peroxidation (HNE) by immunofluorescence. Senescent EC displayed both telomeric instability markers (RFL shortening and increase in ATM, p<0.05) and oxidative stress markers (HNE and Cav‐1, p<0.05). mRNA levels of p53 were directly associated with the DNA damage response protein ATM and p21 (p<0.05) but not with Cav‐1 or HNE (p>0.05), suggesting that senescence is not exclusively directed by SIS. In conclusion, our data suggest that in human EC exposed to risk factors for CVD, there is a significant interplay between replicative senescence and SIS due to a state of cumulative cell damages. This study was supported by the Canadian Institutes of Health Research and the Fonds de la Recherche en Santé du Québec.
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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".