title: Effect of shear stress, statins and TNF-α on hemostatic genes in human endothelial cells.
abstract: Atherosclerotic plaque formation and progression are dependent on local shear stress patterns and inflammatory cytokines. Statins effectively reduce the progression of atherosclerosis and the incidence of cardiovascular events. However, the benefit of statins cannot be explained by cholesterol reduction alone. This study, investigated the non-lipid lowering effects of simvastatin and rosuvastatin on endothelial anti- and prothrombotic genes under different biomechanical and inflammatory stress conditions. Endothelial cells responded in a similar way to simvastatin and rosuvastatin. However, they were more sensitive to simvastatin. The statins had anti-inflammatory properties counteracting the TNF-α effect on the hemostatic genes studied. There was no observed synergistic effect between shear stress and simvastatin. Simvastatin had a counteracting effect on t-PA and PAI-1 compared to TNF-α and shear stress. Simvastatin blocked the TNF-α suppressive effect on thrombomodulin and eNOS, irrespective of shear stress. The strong inductive effect of TNF-α on VCAM-1 was counteracted by simvastatin and shear stress in an additive dose-response dependent way.
authors.affiliation: The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicin, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Niklas.Bergh@gu.se
authors.forename: N
authors.initials: N
authors.lastname: Bergh
authors.forename: P
authors.initials: P
authors.lastname: Larsson
authors.forename: E
authors.initials: E
authors.lastname: Ulfhammer
authors.forename: S
authors.initials: S
authors.lastname: Jern
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects* / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D033081:Shear Strength; D019821:Simvastatin / Q000494:pharmacology; D013314:Stress, Mechanical; D010959:Tissue Plasminogen Activator / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin; D010959:Tissue Plasminogen Activator