Abstract 4909: Nox2-Containing NADPH Oxidase Deficiency Protects Against Age-Dependent Inhibition of Neovascularization
Bibliographic record
Abstract
Background: We have previously shown that aging is associated with an impaired angiogenic response following ischemia. Because aging leads to an increased generation of reactive oxygen species (ROS), here we investigated the role of Nox2-containing NADPH oxidase ROS generation for the modulation of neovascularization by aging. Methods: Hindlimb ischemia was surgically induced by femoral artery removal in young (5–7 weeks) and older (9 months) Nox2 −/− and control (Nox2 +/+ ) mice. Results: We found that blood flow recovery is significantly reduced in older compared to younger mice at day 21 after surgery (Doppler flow ratios: 0.51± 0.05 vs. 0.72± 0.05; p<0.05). At the microvascular level, capillary density was also significantly reduced in ischemic muscles of older animals (53.4± 6.3 capillaries/field vs. 82.5± 4.9 capillaries/field; p<0.001). This was associated with a significant increase of oxidative stress levels (nitrotyrosine immunostaining) in ischemic tissues of older animals. Importantly, we found that Nox2 deficiency reduces oxidative stress levels in ischemic tissues and restores blood flow recuperation in older animals. Endothelial progenitor cells (EPCs) have been shown to have an important role for postnatal neovascularization. Here we found that the functional activities of EPCs (adhesion to HUVECs, migration) are significantly impaired in old compared to young mice. However, Nox2 deficiency rescues EPCs functional activities in older animals. We also demonstrate an age-dependent pathological increase of oxidative stress levels (DCF-DA, DHE) in EPCs that is not present in Nox2-deficient animals. Conclusion: Nox2-containing NADPH oxidase deficiency protects against age-dependent impairment of neovascularization. Potential mechanisms include reduced ROS generation in ischemic tissues and preserved angiogenic activities of EPCs.
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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) | 0.001 | 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) | 0.005 | 0.001 |
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".