Abstract 272: Impaired Arteriogenesis in Cystathionine Gamma-Lyase (CSE) and Endothelial Nitric Oxide Synthase (eNOS) Mutant Mice
Bibliographic record
Abstract
Introduction: Arteriogenesis is an important process involving remodeling of collateral vasculature during chronic or intermittent tissue ischemia. CSE and eNOS are the two principle enzymes for hydrogen sulfide (H 2 S) and Nitric Oxide (NO) generation. Although role of NO during arteriogenesis is partially known, the role of CSE dependent H 2 S production during arteriogenesis remains unknown. Hypothesis/objective: We sought to determine the role of CSE generated H 2 S on arteriogenesis activity of CSE knockout (CSEKO) mice compared to eNOS knock out (eNOSKO) and wild type (WT) mice during hind limb ischemia. Method: Permanent unilateral hind limb ischemia was induced in 12-week-old CSE KO, eNOS KO, and WT mice and studied until day 21. Tissue perfusion was measured using indicator dye blush rates with the SPY Imager system over time along with laser doppler flowmetry. Temporal development of arterial remodeling was also observed using SPY imaging, and vessel number, length and branch morphometry determined over time. Microfil vascular casting was performed to further examine the number of collaterals in ischemic muscles at the end of the study. Histological arteriogenesis was evaluated by vascular smooth muscle actin (SMA) positive vessel density with dual fluorescence staining of anti-CD31 (endothelial positive cell) and anti-α-SMA antibodies. Results: Tissue perfusion was significantly impaired in CSE KO and eNOS KO mice compared to WT mice at different time points throughout the study period. Both CSE KO and eNOS KO mice showed significantly less blush rate than WT mice. SMA positive vessel density was also significantly less in CSE KO and eNOS KO mice than that in WT mice. Conclusion: CSE generated H 2 S and eNOS derived NO play important roles in regulating ischemic arterial remodeling as demonstrated in our studies. The mechanism of impaired arteriogenesis in both mutant mice and the interaction between these two gasotransmitters has yet to be elucidated.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".