Simvastatin Increases Endothelial Nitric Oxide Synthase Expression in Cultured Endothelial Cells Preconditioned with Steady Laminar Flow
Bibliographic record
Abstract
Introduction Statins (HMG‐CoA reductase inhibitors) are known to have benefits in vascular biology beyond lipid reduction. It has been reported that statins can elevate the expression of endothelial nitric oxide synthase (eNOS) in cultured endothelial cells; however, it is not known whether this increase is conserved under hemodynamic stimulation. Methods and Results Human abdominal aortic endothelial cells were pre‐conditioned with fluid shear stress (1, 10 or 20 dynes/cm 2 ) for 6 h. Without stopping the perfusion, control vehicle, simvastatin or simvastatin with mevalonate were added to the perfusion media and the flow experiment was continued for 24 h. As expected, eNOS mRNA and protein increased with increasing levels of fluid shear stress. Treatment with 1 or 10 µM of simvastatin further elevated eNOS mRNA and protein. Co‐incubation with mevalonate, a precursor to cholesterol synthesis, eliminated the effect of the statin, but had no effect on shear induction of eNOS. This suggests that the effect of statins on eNOS expression is conserved under flow and that the mechanism in which simvastatin induces eNOS is through inhibition of HMG‐CoA reductase. Conclusions Simvastatin enhances eNOS expression in cultured endothelial cells pre‐conditioned with steady laminar flow through inhibition of HMG‐CoA reductase. These results may explain the benefits of statins in the clinic beyond lipid reduction.
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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) | 0.001 | 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) | 0.003 | 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".