Impairment of Vascular Function in a Mouse Model of Neurofibromatosis Type 1
Bibliographic record
Abstract
Neurofibromatosis 1 (NF1) is an autosomal dominant disorder, characterized by multiple café‐au‐lait spots, iris harmartomas, multiple nerve sheath tumors. Patients also present with heart and cerebrovascular disease, ischemia, or aneurysm. Though vasculopathy is well documented in NF1 patients, the pathophysiology is poorly understood. The objective of this study was to investigate the function and structural integrity of the thoracic aorta in a well‐established mouse model of NF1 (6‐month old). We observed a significant increase in contraction in response to depolarization of vascular smooth muscle and endothelial cells in Nf1 +/‐ mice, but diminished contraction in response to phenylephrine. Interestingly, endothelium‐dependent relaxation was significantly higher in Nf1 +/‐ mice, which was completely inhibited by the nitric oxide synthase (NOS) inhibitor, suggesting the relaxation results from nitric oxide (NO) production. Consistent with increased NO production, protein expression of endothelial NOS (eNOS), phospho‐eNOS, and the phospho‐Akt were increased in Nf1 +/‐ aorta. Histological examination revealed that alteration in aortic function is also associated with elastin fiber disorganization within the aortic wall. This study, for the first time, underscores the pathological events underlying vascular complications in NF1, shedding light on potential new therapeutic targets to address vascular dysfunctions in NF1 patients. The presented study was funded by the Children's Tumor Foundation and the Canadian Institutes of Health Research.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".