Abstract 377: Soluble CD40 Ligand Reverses the Inhibitory Effect of Early Endothelial Progenitor Cells on Platelet Aggregation
Bibliographic record
Abstract
Introduction and hypothesis: Circulating Endothelial progenitor cells (EPCs) interact with other blood cells and platelets and may contribute to limit the thrombo-inflammatory reactions at the sites of vascular injury. Indeed, we have previously shown that EPCs inhibit platelet activation and aggregation. The CD40/CD40L axis is a thrombo-inflammatory mediator that affects platelet and endothelial functions. EPCs express CD40 while platelets represent the major source of soluble CD40 ligand (sCD40L) in the circulation. We aimed to demonstrate the existence of a sCD40L/CD40 signaling pathway in EPCs and to test the hypothesis that sCD40L affects the anti-platelet function of EPCs. Methods and results: Human peripheral blood mononuclear cell-derived early EPCs in culture express CD40 and its adaptor proteins, the tumor necrosis factor associated factors: TRAF1, TRAF2 and TRAF3. sCD40L stimulation of early EPCs had no effect on TRAF2 expression, but increased its binding to CD40. In contrast, sCD40L increased the expression of TRAF1 and affected its binding to CD40; whereas TRAF3 binding was not affected. In functional studies, pretreatment of early EPCs with sCD40L had no effect on their viability, but reduced their inhibitory effect on platelet aggregation. However, the release of the anti-aggregating agents prostacyclin and nitric oxide by early EPCs was not affected by sCD40L treatment. Conclusion: We have revealed the existence of the CD40L/CD40/TRAF axis in early EPCs, which reduced their anti-platelet properties. This was not related to an effect of sCD40L on early EPC survival nor on their release of prostacyclin or nitric oxide.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".