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Updated: Apr 9, 2026
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
The effect of simvastatin treatment on endothelial cell response to shear stress and tumor necrosis factor alpha
Melissa Dick1,2, Katherine MacDonald3, Jean-Claude Tardif4
1Department of Chemical Engineering, McGill University, 3610 University Avenue, Montreal, QC, H3A 2B2, Canada. melissa.dick@mail.mcgill.ca.
Insights
Statin drugs alter endothelial cell (EC) shape to a rounded, atheroprone morphology. However, ECs still respond to blood flow (wall shear stress), suggesting potential for targeted therapies.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Biology
- Pharmacology
Background:
- Statins are widely prescribed cholesterol-lowering drugs.
- Statin pleiotropic effects on endothelial cells (ECs) are not fully understood.
- The influence of blood flow on EC response to statins requires further investigation.
Purpose of the Study:
- To investigate the effects of statin treatment on EC morphology and cytoskeletal structure.
- To examine how tumor necrosis factor alpha (TNF-α) and wall shear stress (WSS) modulate EC response to statins.
- To understand the interplay between statins, inflammation, and hemodynamics in ECs.
Main Methods:
- Endothelial cells were treated with statins and/or TNF-α.
- A 3D tissue culture model subjected ECs to physiologically relevant wall shear stress (12.5 dynes/cm²).
- Cell morphology, cytoskeletal structure, and alignment were analyzed using microscopy; statistical analyses were performed.
Main Results:
- Statin treatment induced a rounded, atheroprone EC morphology (increased shape index).
- TNF-α stimulation promoted an elongated, atheroprotective EC morphology (decreased shape index).
- Neither WSS nor TNF-α reversed statin-induced cell rounding or F-actin disruption.
Conclusions:
- Statin treatment results in an atheroprone EC morphology despite potentially atheroprotective genotypes.
- TNF-α induces an atheroprotective morphology but an atheroprone genotype.
- ECs maintain responsiveness to WSS despite statin or TNF-α-induced morphological changes, indicating potential therapeutic targets.
Background:
Statin drugs are one of the most commonly prescribed pharmaceuticals by physicians. By blocking the rate-limiting step in the cholesterol biosynthesis pathway, statins inhibit cholesterol synthesis, which benefits patient health. However, since many other important cellular processes are regulated within this pathway, they may also be influenced by statin therapy. These pleiotropic effects of statins have not been fully investigated, but are believed to positively influence endothelial cells (ECs), which line the vasculature in a confluent monolayer. Few studies have considered the effect of blood flow on ECs and how this may augment EC response to statins.
Methods:
In this study, the effect of statin treatment on ECs is investigated for cells stimulated with tumor necrosis factor alpha (TNF-α), an inflammatory cytokine that promotes an atheroprone endothelium. Additionally, ECs are exposed to a physiologically relevant wall shear stress (WSS) of 12.5 dynes/cm(2) using a three-dimensional tissue culture model to provide a realistic hemodynamic environment. ECs are analyzed for morphology using light microscopy as well as cytoskeletal structure and alignment using confocal microscopy. Statistical analysis is performed on the results using both the one-way analysis of variance with Bonferroni post-tests and the two-tailed t test.
Results:
We have shown that statin treatment caused cells to adapt to a rounded, atheroprone morphology, with a significantly higher shape index. Oppositely, TNF-α stimulation caused cells to elongate to an atheroprotective morphology, with a significantly lower shape index. WSS and TNF-α were unable to reverse any statin-induced cell rounding or F-actin disruption.
Conclusion:
Further work is therefore needed to determine why statin drugs cause cells to have an atheroprone morphology, but an atheroprotective genotype, and why TNF-α stimulation causes an atheroprotective morphology, but an atheroprone genotype. Despite the morphological changes due to statins or stimulation, ECs still respond to WSS. Understanding how statins influence ECs will allow for more targeted treatments for hypercholestemia and potentially other diseases.
