Abstract 600: Neonatal Transient Hyperoxic Exposure Leads to Persistent Vascular DNA Damage and Increased Senescence Proteins in Rats: Potential Role in Developmental Programming of Hypertension
Bibliographic record
Abstract
Background: Preterm infants have reduced antioxidant defenses vs. babies born at term and are exposed to high levels of oxygen (O2) both in intensive care and as compared to the intrauterine environment. We have shown that neonatal hyperoxic stress leads in adult rats to hypertension, endothelial dysfunction and arterial rigidity, all characteristic of vascular aging. Indeed, acutely, markers of vascular cells senescence are increased. Aim: To examine whether indices of vascular aging persists beyond neonatal hyperoxic exposure. For this purpose, vessels (aorta) are studied at 4 weeks (wks, pre-hypertension) and 16 wks (young adults-elevated blood pressure). Methods: Sprague-Dawley pups were kept at 80% O2 or in room air from postnatal days 3 to 10. Aortas were sampled at 4 and 16 wks (n=5-7 animals/group) to examine tumour suppressor p53 binding protein 1 (53BP1, indices of DNA damage) and senescence proteins (p53, p16 and p21) by immunofluorescence. Bax and bcl2 proteins (for apoptosis) were assessed by western blot at 4 wks. Results: At 4 wks, aortas of O2 exposed rats showed increased nuclear foci of 53BP1 (19.3±0.8 vs. 10.5±1.1 fluorescence intensity, p<0.0001), and increased expression of p53 (19.3±0.4 vs. 16.3±0.9, p<0.05) compared to controls. Expressions of Bax (pro-apoptotic protein) and the ratio Bax/Bcl2 were not different between groups (2±0.2 vs. 1.6±0.1, and 1.4±0.1 vs. 1.2±0.1, respectively). Bcl2 (anti-apoptotic protein) was decreased in O2 exposed rats compared to controls (1.6±0.03 vs. 1.3±0.07, p<0.01). At 16 wks, O2 exposed rats showed also increased nuclear foci of 53BP1 (23.9±3.8 vs. 14.2±0.9, p<0.05), and increased expression of p53 (21.6±1.6 vs. 13.8±0.5, p<0.01), and p16 (16.9±1.6 vs. 7.7±0.8, p<0.01), p21 was not changed (11.5±0.9 vs. 14±1.9, non significant). Conclusions: Neonatal exposure to O2 leads at 4 wks and 16 wks to DNA damage and expression of senescence associated proteins without evidence of apoptosis (at 4wks ). These changes are present before the adult consequences of neonatal exposure (i.e. hypertension and vascular dysfunction) and may contribute to their development.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".