cAMP‐signaling regulates the expression of atheroprotective genes in vascular endothelial cells exposed to differential fluid shear stresses (851.14)
Bibliographic record
Abstract
Fluid‐mediated shear stress is an important, but often overlooked, mediator of vascular endothelial cell (VEC) health. VECs in the linear portions of macrovascular structures experience high laminar shear stress and exhibit an anti‐inflammatory and anti‐thrombotic phenotype. However, at vascular bifurcations and large curvatures fluid shear stress dramatically declines. Exposure to this low shear stress reduces VEC expression of vasculoprotective genes, making these areas preferential targets of atherosclerosis development. cAMP‐signaling is known to regulate a diverse array of VEC functions. Using various methodologies, we investigated the role of cAMP, and its downstream effectors, protein kinase A (PKA) and exchange protein activated by cAMP (EPAC)‐1, in regulating VEC health under differential fluid shear stresses. We report a novel role for cAMP, where modulation of this signaling pathway alters the expression of both atheroprotective and inflammatory genes in high and low shear stress conditions. This work has very important therapeutic implications for diseases characterized by endothelial cell dysfunction and atherosclerosis. Grant Funding Source : Canadian Institutes of Health Research
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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 | 0.002 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".