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Simvastatin alters human endothelial cell adhesion molecule expression and inhibits leukocyte adhesion under flow

Eccles, KA; Sowden, H; Porter, KE; Parkin, SM; Homer-Vanniasinkam, S; Graham, AM; (2008) Simvastatin alters human endothelial cell adhesion molecule expression and inhibits leukocyte adhesion under flow. ATHEROSCLEROSIS , 200 (1) 69 - 79. 10.1016/j.atherosclerosis.2007.12.018.

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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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Type:Article
Title:Simvastatin alters human endothelial cell adhesion molecule expression and inhibits leukocyte adhesion under flow
DOI:10.1016/j.atherosclerosis.2007.12.018
Keywords:simvastatin, inflammation, endothelial cells, cell adhesion molecules, in vitro laminar flow, COA-REDUCTASE INHIBITORS, NITRIC-OXIDE SYNTHASE, RHO GTPASE, ATHEROSCLEROSIS, STATINS, DISEASE, ICAM-1, ALPHA, ATORVASTATIN, METABOLISM
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)

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