Epidermal Growth Factor-Like Domain 7 Suppresses Intercellular Adhesion Molecule 1 Expression in Response to Hypoxia/Reoxygenation Injury in Human Coronary Artery Endothelial Cells
Bibliographic record
Abstract
BACKGROUND: Epidermal growth factor-like domain 7 (Egfl7) is a chemoattractant for endothelial cells, and its expression is restricted to endothelial cells. Hypoxia/reoxygenation (H/R) induced endothelial injury that occurs during transplantation contributes to the subsequent development of allograft vasculopathy. We investigated the effect of Egfl7 on endothelial cell intercellular adhesion molecule 1 expression in response to H/R injury. METHODS AND RESULTS: Human coronary artery endothelial cells were submitted to hypoxia (0.1% O(2)) followed by normoxia (21% O(2)) in the presence or absence of Egfl7 (100 ng/mL). Hypoxia alone increased the expression of Egfl7×140±8% of control at 3 hours (n=6; P<0.05) and 385±50% of control at 6 hours (n=6; P<0.001). Incubation with Egfl7 during the reoxygenation period prevented intercellular adhesion molecule 1 upregulation (mean fluorescence intensity: 5.37±0.92 versus 3.81±0.21; P<0.05; n=4 per group). Nuclear factor-κB nuclear localization on H/R injury was blocked by Egfl7 administration (cytosolic/nuclear ratio of 0.93±0.01 versus 1.44±0.24; P<0.05; n=4 per group). Inhibitor of nuclear factor-κB protein level was significantly reduced on H/R injury (26±4.6% of control expression; P<0.05; n=4 per group); however, concurrent incubation with Egfl7 attenuated this reduction (46±6.2% of control expression; P<0.05 when compared with H/R injury alone; n=4 per group). CONCLUSIONS: Our study reveals the novel observation that hypoxia upregulates human coronary artery endothelial cells expression of Egfl7 and that Egfl7 inhibits expression of intercellular adhesion molecule 1 subsequent to H/R injury. Mechanistically, Egfl7 prevented nuclear factor-κB nuclear localization and augmented inhibitor of nuclear factor-κB protein levels, suggesting that it inhibits nuclear factor-κB activation, a key step in the inflammatory activation of endothelial cells. Egfl7 may be protective against H/R injury incurred during transplantation and may modulate the events that lead to the development of graft vasculopathy.
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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".