Nestin downregulation in rat vascular smooth muscle cells represents an early marker of vascular disease in experimental type I diabetes
Bibliographic record
Abstract
BACKGROUND: Nestin was reported to directly contribute to cell proliferation and the intermediate filament protein was detected in vascular smooth muscle cells. In experimental type I diabetes, nestin downregulation in the heart was identified as an incipient pathophysiological event. The following study tested the hypothesis that dysregulation of nestin expression in vascular smooth muscle cells represented an early event of vascular disease in experimental type I diabetes. METHODS/RESULTS: In the carotid artery and aorta of adult male Sprague-Dawley rats, a subpopulation of vascular smooth muscle cells co-expressed nestin and was actively involved in the cell cycle as reflected by the co-staining of nuclear phosphohistone-3. The infection of aortic vascular smooth muscle cells with a lentivirus containing a shRNAmir directed against nestin significantly reduced protein expression and concomitantly attenuated basal DNA synthesis. Two weeks following injection of adult male Sprague-Dawley rats with streptozotocin, the endothelial response of aortic rings to acetylcholine, vascular morphology and the total density of vascular smooth muscle cells in the vasculature of type I diabetic rats were similar to normal rats. By contrast, nestin protein levels and the density of nestin(+)/phosphohistone-3(+)-vascular smooth muscle cells were significantly reduced in type I diabetic rats. The in vivo observations were recapitulated in vitro as exposure of vascular smooth muscle cells to 30 mM D-glucose inhibited DNA synthesis and concomitantly reduced nestin protein expression. CONCLUSIONS: Hyperglycaemia-mediated nestin downregulation and the concomitant reduction of cycling vascular smooth muscle cells represent early markers of vascular disease in experimental type I diabetes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".