Abstract 15947: Transient Neonatal Exposure to High Oxygen Levels is Associated With Impaired Ischemia-induced Neovascularization During Adulthood
Bibliographic record
Abstract
Introduction: Deleterious perinatal conditions, including preterm birth, can lead to developmental programming of cardiovascular diseases. Prematurely born infants are often exposed to high oxygen levels, which in animal models has been associated with the adult development of endothelial dysfunction, hypertension, and cardiac remodeling. Here we tested the novel hypothesis that neonatal exposure to hyperoxia might impair ischemia-induced neovascularization in the adult. Methods and Results: C57Bl/6 newborn mice were kept with their mother in 85% O 2 or room air (control) from day 2 to 14 after birth. When the mice reached adulthood (6-8 weeks), hindlimb ischemia was surgically induced by femoral artery removal. Neonatal exposure to O 2 was not associated with hypertension in adult mice. However mice exposed to O 2 after birth showed a significant impairment of blood flow recovery after hindlimb ischemia, as assessed by Laser Doppler imaging at day 7 and 21 after surgery. Clinically, this was also associated with increased hindlimb ischemic damages. At the microvascular level, neonatal hyperoxia was associated with a significant decrease of capillary density in ischemic muscles. Moreover, ischemic muscles isolated from mice exposed to O 2 exhibited increased oxidative stress levels (DHE staining), together with a reduced expression of superoxide dismutase 1 (SOD1) and vascular endothelial growth factor (VEGF), as assessed by Western blotting. Pro-angiogenic cells (PACs) have been shown to have an important role for postnatal neovascularisation. Here we found that neonatal exposure to O 2 is associated with a significantly reduced number of central (bone marrow) and peripheral PACs in adults. Interestingly, the functional/angiogenic activities of both PACs and mature mouse aortic endothelial cells (MAECs) are significantly impaired in mice that have been exposed to O 2 after birth. Conclusions: Transient neonatal exposure to high oxygen levels leads to impaired ischemia-induced neovascularization during adulthood. The mechanism involves negative effects of neonatal hyperoxia on oxidative stress levels and angiogenic signals in ischemic muscles, together with defective functional activities of PACs and mature endothelial cells.
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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) | 0.001 | 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) | 0.003 | 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".