Abstract 5493: Heparan-Sulfate Deficient Perlecan Mice Exhibit Increased Vascular Smooth Muscle Cell Activity and Response to Arterial Injury
Bibliographic record
Abstract
Percutaneous coronary interventions (PCI) are limited by restenosis, a process that involves smooth muscle cell (SMC) proliferation and migration. Perlecan, a heparan-sulfate proteoglycan present in the vessel wall has been shown to inhibit SMC activity in vitro, and decrease intimal hyperplasia in animal models of arterial injury. As well, heparinase treatment of perlecan results in a loss of these inhibitory effects in vitro. This study examined the hypothesis that heparan sulfate (HS) has an inhibitory role in perlecan’s regulation of SMC activity. Aortic SMC from transgenic mice expressing HS-deficient Perlecan (M Δ3/Δ3 ) and control (WT) mice were isolated and cultured to characterize SMC activity. Additionally, M Δ3/Δ3 and control mice underwent a carotid artery wire injury and carotid arteries were harvested 1 week (n=6) and 3 weeks (n=12) post-surgery for histological analysis. Over 7 days, M Δ3/Δ3 cells showed significantly higher proliferation during the log phase (days 2–4), with almost a 2-fold increase in cell density during the plateau phase (days 5–7), compared to WT SMC (p<0.001). Incubation with FGF-2 or PDGF-BB resulted in significantly greater M Δ3/Δ3 cell density versus WT (p<0.001). PDGF-BB induced migration was also significantly greater in the M Δ3/Δ3 cells (216.2 ± 2.81) than the WT cells (151.9 ± 2.97) (p<0.01). Following arterial injury, significant medial thickening was seen at 1 and 3 weeks, in WT and M Δ3/Δ3 arteries. Increases in medial thickness of M Δ3/Δ3 arteries were significantly greater than those seen in WT arteries at all respective time points (p<0.001). In conclusion, the differences seen in SMC activity and response to arterial injury between WT and M Δ3/Δ3 populations demonstrate that the HS side chains play a critical role in perlecan’s inhibitory effects of SMC activity, and may indicate a promising therapeutic target for the prevention of restenosis following PCI.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.011 | 0.003 |
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".