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Updated: Jul 5, 2026
Imaging Leukocyte Adhesion to the Vascular Endothelium at High Intraluminal Pressure
Published on: August 23, 2011
Simvastatin alters human endothelial cell adhesion molecule expression and inhibits leukocyte adhesion under flow
Kirstie A Eccles1, Heather Sowden, Karen E Porter
1Centre for Atherothrombosis Research, Bradford University, BD7 1DP, United Kingdom. K.Eccles@bradford.ac.uk
Insights
Statins reduce inflammatory cell interactions with endothelial cells (EC), independent of lipid lowering. This suggests anti-inflammatory mechanisms contribute to statins' cardiovascular benefits by improving EC function.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Cell Biology
Background:
- Hypercholesterolemia is a key risk factor for atherosclerosis.
- Statins, primarily used for lipid lowering, exhibit pleiotropic effects that reduce cardiovascular events.
- Endothelial cell (EC) dysfunction is central to atherosclerosis pathogenesis.
Purpose of the Study:
- To investigate the anti-inflammatory effects of statins on endothelial cells.
- To elucidate the mechanisms by which statins may improve endothelial function.
Main Methods:
- Functional responses of human umbilical vein endothelial cells (HUVEC) and neutrophils were studied under physiological flow.
- Cell interactions (tethering, rolling) were quantified after stimulation with histamine or TNF-alpha, with and without statin pre-treatment.
- Surface expression of P- and E-selectin was measured using ELISA.
Main Results:
- Statin pre-treatment significantly reduced histamine-induced neutrophil-EC tethering and TNF-alpha-induced rolling.
- Mevalonate reversed the statin-mediated reduction in cell interactions.
- Statin pre-treatment abrogated histamine-induced P-selectin and reduced TNF-alpha-induced E-selectin expression on EC.
Conclusions:
- Statins possess anti-inflammatory properties on endothelial cells, independent of lipid-lowering.
- These effects are mediated, at least in part, by inhibiting selectin expression.
- The anti-inflammatory actions of statins may contribute significantly to their cardiovascular protective effects.
Abstract:
Hypercholesterolaemia is implicated as an independent risk factor in the pathogenesis of atherosclerosis. HMG-CoA reductase inhibitors (statins) are prescribed for their lipid-lowering effects but recent evidence suggests they have pleiotropic effects independent of lipid balance regulation that may explain their role in dramatically decreasing cardiovascular mortality and morbidity. The mechanisms responsible are unclear but endothelial cell (EC) dysfunction is critical. To investigate potential anti-inflammatory properties of statins on EC, functional responses of human umbilical vein endothelial cells (HUVEC) and human neutrophils under physiological flow conditions were studied. These interactions were quantified in response to inflammatory mediators following pre-treatment with statin. Histamine stimulation resulted in significant (p<0.001) increases in transient interactions between neutrophils and EC (tethering). These effects were significantly reduced (p<0.001) on pre-treatment with statin. TNF-alpha stimulation resulted in significant (p<0.001) increases in rolling interactions. These effects were significantly (p<0.001) reduced following pre-treatment of EC with statin. Mevalonate pre-treatment of EC significantly reversed the effects of statin pre-treatment on both tethering and rolling (p<0.001). Reductions in surface expression of P- and E-selectin were confirmed by ELISA. EC exposed to histamine demonstrated significantly increased (p<0.01) levels of P-selectin, abrogated (p<0.001) by pre-treatment with statin. EC exposed to TNF-alpha demonstrated a significant increase (p<0.001) in levels of E-selectin, reduced (p<0.05) by pre-treatment with statin.
