The Response of Human Aortic Endothelial Cells in a Stenotic Hemodynamic Environment: Effect of Duration, Magnitude, and Spatial Gradients in Wall Shear Stress
Bibliographic record
Abstract
Inflammation plays a key role in the development and stability of coronary plaques. Endothelial cells alter their expression in response to wall shear stress (WSS). Straight/tubular and asymmetric stenosis models were designed to study the localized expression of atheroprone molecules and inflammatory markers due to the presence of the spatial wall shear stress gradients created by an eccentric plaque. The effects of steady wall shear stress duration (0-24 h) and magnitude (4.5-18 dynes/cm(2)) were analyzed in human abdominal aortic endothelial cells through quantitative real-time polymerase chain reaction (PCR) and immunofluorescence analysis in straight/tubular models. Regional expression was assessed by immunofluorescence and confocal microscopy in stenosis models. Under steady fully developed flow, endothelial cells exhibited a sustained increase in levels of atheroprotective genes with WSS duration and magnitude. The local response in the stenosis model showed that expression of endothelial nitric oxide synthase and Kruppel-like factor 2 is magnitude rather than gradient dependent. A WSS magnitude dependent transient increase in translocation of transcription factor nuclear factor kappaB was observed. Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin exhibited a sustained increase in protein expression with time. The mRNA levels of these molecules were transiently upregulated and this was followed by a decrease in expression to levels lower than static controls. Regionally, increased inflammatory marker expression was observed in regions of WSS gradients both proximal and distal to the stenosis when compared with the uniform flow regions, whereas the atheroprotective markers were expressed to a greater extent in regions of elevated WSS magnitudes. The results from the straight/tubular model cannot explain the regional variation seen in the stenosis models. This may help explain the localization of inflammatory cells at the shoulders of plaques in vivo.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".