The effect of statins on endothelial cell response to wall shear stress in three dimensional in vitro tissue culture models
Bibliographic record
Abstract
High blood cholesterol is a primary risk factor for cardiovascular diseases such as atherosclerosis. Atherosclerosis is a disease in which white blood cells, lipids (including cholesterol), and other cellular debris build up within the blood vessel walls to cause vessel inflammation and narrowing, ultimately leading to heart attack or stroke. Statin drugs, inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, were designed to inhibit cholesterol synthesis by preventing the conversion of HMG-CoA to mevalonate within the cholesterol biosynthesis pathway. Although clinically effective at reducing circulating levels of cholesterol, statins have also been shown to have other beneficial effects, termed pleiotropic effects. Researchers believe that these pleiotropic effects are caused by the positive influence of statins on endothelial cells, the inner most layer of the vasculature that is constantly exposed to fluid wall shear stress.This work studied the cumulative effect of statin therapy and wall shear stress on endothelial cell structure and function using a three dimensional, in vitro tissue culture model. Endothelial cells were cultured within the model and exposed to 12.5 dynes/cm2 of wall shear stress and treated with the statin drug simvastatin for 24 hours. Endothelial cell morphology, F-actin cytoskeleton arrangement, and neutrophil adhesion to endothelial cells were analyzed.Statins caused endothelial cells to conform to a rounded, unhealthy phenotype, which was not reversed by the presence of wall shear stress. The F-actin cytoskeleton of the endothelial cells was disrupted by statin treatment, also non-reversible by wall shear stress. There was no conclusive evidence that statin therapy affected neutrophil adhesion, although wall shear stress significantly decreased adhesion. The addition of mevalonate reversed all statin effects, confirming statin regulation through the cholesterol biosynthesis pathway. Understanding how statin therapy affects endothelial cells in the presence of wall shear stress may allow for improved treatment options or more specific statin drugs in the future.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".