Effect of shear stress, statins and TNF-alpha on hemostatic genes in human endothelial cells

• 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-alpha 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-alpha and shear stress. Simvastatin blocked the TNF-alpha suppressive effect on thrombomodulin and eNOS, irrespective of shear stress. The strong inductive effect of TNF-alpha on VCAM-1 was counteracted by simvastatin and shear stress in an additive dose-response dependent way.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Cells

Cultured

Dose-Response Relationship

Drug

Gene Expression Regulation/*drug effects

Hemostasis/*drug effects/genetics

Human Umbilical Vein Endothelial Cells/*drug effects/metabolism

Humans

Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology

*Shear Strength

Simvastatin/pharmacology

*Stress

Mechanical

Tissue Plasminogen Activator/genetics

Tumor Necrosis Factor-alpha/*pharmacology

Publikations- och innehållstyp

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