Effects of vascular endothelial growth factor on endothelin-1 production by human lung microvascular endothelial cells in vitro
Bibliographic record
Abstract
AIMS: Increased endothelin-1 (ET-1) is a hallmark of pulmonary arterial hypertension (PAH), and contributes to its pathogenesis. The factors controlling ET-1 in PAH are poorly understood. Combined with other stimuli, vascular endothelial growth factor (VEGF) blockade results in PAH-like lesions in animal models, and has been associated with PAH in humans. The effects of VEGF on ET-1 production by human lung blood microvascular endothelial cells (HMVEC-LBl) are unknown. MAIN METHODS: We exposed HMVEC-LBl in-vitro to human VEGF-121 (40 ng/mL) in serum-free medium for 7h, in the absence or presence of the VEGF receptor antagonist, SU5416 (3 and 10 μM). ET-1 production was measured in the supernatant. Phosphorylation of VEGF receptor 2 (VEGFR2) was measured by Western blotting after exposure to VEGF without or with SU5416 for 5 and 10 min. KEY FINDINGS: VEGF effectively caused VEGFR2 phosphorylation, which was blocked by SU5416. VEGF decreased ET-1 production by at least 29%. In the absence of VEGF, SU5416 increased ET-1 production, by 16% at 10 μM, and SU5416 was able to completely abolish the VEGF effect on ET-1 production. SIGNIFICANCE: VEGF may promote vascular health by decreasing ET-1 production in HVMEC-LBl. Blockade of VEGF signaling by SU5416 increases ET-1 levels. The role of VEGF in modulating endothelin production in PAH deserves further study.
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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 | 0.001 |
| 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".