Effects of two complex hemodynamic stimulation profiles on hemostatic genes in a vessel-like environment.
Endothelial cells are the main sensors of changes in the biomechanical flow environment and play a pivotal role in vascular homeostasis. An in vitro perfusion model was developed to study the regulatory effect on gene expression by different flow and pressure profiles. Human umbilical vein endothelial cells were grown to confluence inside capillary microslides or silicone tubes. Thereafter, they were exposed to different levels of shear stress or different levels of static or pulsatile pressure. Genes representing various hemostasis functions of the endothelial cells were analyzed. Shear stress was a more effortful stimulus than static or pulsatile tensile stress. Although shear stress affected mRNA expression of all six studied genes (tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor [PAI]-1, Thrombomodulin [TM], urokinase-type plasminogen activator [u-PA], vascular cell adhesion molecule [VCAM-1], and endothelial nitric oxide synthase [eNOS]), none of the genes was found regulated by pressure. Shear stress down-regulated t-PA and VCAM-1 in a dose response-dependent way, and up-regulated TM. u-PA, eNOS, and PAI-1 were up-regulated by shear stress, but there was no obvious dose-response effect for these genes. These findings suggest that shear stress has a more powerful gene regulatory effect on endothelial gene expression than tensile stress. Low shear stress induced a more proatherogenic endothelial surface but preserved t-PA gene expression levels compared to high shear stress.
Bergh
N
N
Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, The Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Ulfhammer
E
E
Karlsson
L
L
Jern
S
S
D001794:Blood Pressure / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006439:Hemodynamics / Q000235:genetics*; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology; D018180:Thrombomodulin / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D052250:Nitric Oxide Synthase Type III; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator