Opposing effect of angiopoietin‐1 on VEGF‐mediated disruption of endothelial cell–cell interactions requires activation of PKCβ
Bibliographic record
Abstract
Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) cooperate in migration and survival of endothelial cells by activation of phosphatidylinositol-3 (PI-3) kinase and mitogen activating protein (MAP) kinase pathways. However, Ang1 opposes the effect of VEGF on vascular permeability. We found that Ang1 also blocks VEGF-mediated diffusion of fluoresin isothiocyanate (FITC)-labeled albumin across an endothelial cell monolayer. VEGF-mediated vascular permeability has been attributed, in part, to activation of phospholipase A(2) and subsequent formation of platelet activating factor. However, Ang1 had no effect on VEGF-induced activation of phospholipase A(2) or the release of arachidonic acid. VEGF-mediated permeability was associated with disruption of endothelial cell junctional complexes, dissociation of beta-catenin from VE-cadherin, and accumulation of beta-catenin in the cytosol. In contrast, Ang1 enhanced the interaction of beta-catenin with VE-cadherin and impaired VEGF-mediated dissociation of this complex. Ang1 also blocked VEGF-induced translocation of protein kinase C (PKC) and beta2 to the membrane, but had no effect on activation of PKC alpha. In addition, staurosporine and a PKC beta inhibitor, LY379196, blocked VEGF-mediated dissociation of beta-catenin from VE-cadherin, diffusion of albumin across the endothelial cell monolayer, and translocation of PKC beta isoforms. These data indicate that VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta isoforms and that this pathway is blocked by Ang1.
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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 | 0.000 | 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 | 0.000 |
| 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".