Hypoxia Results in Upregulation and De Novo Activation of Von Willebrand Factor Expression in Lung Endothelial Cells
Bibliographic record
Abstract
OBJECTIVE: Increased von Willebrand factor (VWF) levels in lungs are associated with diseases such as pulmonary hypertension. The objective of our study was to determine the mechanism of increased VWF levels in conditions, such as hypoxia, which contribute to pulmonary hypertension. APPROACH AND RESULTS: We have previously reported generation of transgenic mice that express LacZ transgene under the regulation of lung- and brain-specific transcriptional regulatory elements of the VWF gene. Hypoxia exposure of these transgenic mice resulted in increased VWF and LacZ mRNA levels as well as redistribution of their expression from primarily larger vessels in the lungs to microvessels. Exposure of cultured lung microvascular endothelial cells to hypoxia demonstrated that VWF upregulation was accompanied by increased platelet binding. Transcription upregulation was mediated through inhibition of the repressor nuclear factor-IB association with the VWF promoter, and increased nuclear translocation of the transcription factor YY1 and association with its cognate binding site on the VWF gene. Knockdown of YY1 expression abolished the hypoxia-induced upregulation and reduced basal level of VWF. CONCLUSIONS: These analyses demonstrate that hypoxia induces a phenotypic shift, accompanied by modulation of nuclear factor-IB and YY1 activities, in microvascular endothelial cells of the lungs to support VWF promoter activation.
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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".