PB0808 Localized Endothelial Colony-Forming Cell-Derived von Willebrand Factor (VWF) Influences In Vivo Angiogenesis in VWF-Deficient Mice
Bibliographic record
Abstract
Background: Flow based assays are commonly used to investigate the function of VWF, however results can vary due to the type of surface coating used and the source and concentration of VWF used.Aims: To investigate different parameters affecting flow assays to probe VWF function.Methods: Ibidi VI0.1 chambers were coated collagen and perfused with whole blood from healthy donors, or plasma free blood (PFB) supplemented with plasma derived or recombinant VWF.VWF mediated platelet capture was measured as platelet surface coverage (PSC).A panel of VWD causing mutations were generated and expressed in HEK293T cells.Results: Larger, more discrete thrombi formed when whole blood was perfused over collagen type I and PSC ranged from 5 to 40% but did not associate with plasma VWF levels.Interestingly while more PSC and larger thrombi were seen at pathological shear rates and did correlate with VWF levels, some individuals demonstrated reduced PSC at high shear rates.When using PFB, although PSC was affected by VWF concentration, even low concentrations of recombinant VWF (0.5 μg/ml) gave good PSC and purified VWF enriched for the highest weight multimers demonstrated less PSC than VWF containing a full range of multimers.With PFB higher background binding in the absence of VWF was seen with collagen type I due to contaminating VWF, while collagen type III gave little or no background binding.As expected type 2M mutations demonstrated reduced PSC, while type 2B mutations caused large rolling aggregates at 1500s-1 that were readily digested by ADAMTS13.Conclusion(s): Together this data confirms the variability in in-vitro thrombus formation and indicates that some individuals do not readily form thrombi at pathological shear rates in-vitro.This work also indicates that when investigating VWF function in flow assays collagen type III should be used and high protein concentrations are not necessary.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".