Objectives In vivo, vascular endothelial cells are constantly subjected to and sensitive to fluid shear stress. Shear stress may be the most crucial local factor affecting atherogenesis. Atherosclerotic lesions preferentially develop at arterial wall sites with low fluid shear stress or turbulent flow, while adjacent regions exposed to laminar flow and high mean shear stress are protected from atherogenesis. This study was designed to investigate the role of shear stress in modulating ox- LDL uptake and its underlying mechanisms in human vascular endothelial cells.
Methods Human umbilical vein endothelial cells (HUVECs) were exposed to 0 dyne/cm2, 5 dyne/cm2, 25 dyne/cm2 fluid shear stress in a parallel flow chamber for 4 hours respectively, while treated with fluorescence- labelled ox- LDL (DiI- ox- LDL, 10 ug/ml) perfusion solution at the same time, mimicing the hypercholesterolemic condition in vivo. HE and Oil Red O staining, scanning electron microscopy, transmission electron microscopy were used to examine the pathological and morphological changes of HUVECs. Immunofluorescence confocal laser scanning and flow cytometry were used to evaluate the ox-LDL endocytosis and integrin β1 protein expression. U937 monocyte adhesion assays were also performed.
Results Under low shear stress conditions, ox- LDL caused severe endothelial cell injury, significant cytoplasmic lipid vacuoles accumulation, marked monocyte adhesion to HUVECs, as well as up-regulation of integrin β1. The exposure of HUVECs to high shear stress resulted in a 25% reduction of ox- LDL uptake (25 dyne/cm2 versus 0 dyne/cm2, P <0.05) thereby in a decrease of cytoplasmic lipid vacuoles, consistent with the downregulation of integrin β1 and suppression of monocyte adhesion to HUVECs.
Conclusions These results indicate the preventive effects of increased shear stress on ox- LDL induced endothelial cell damage. These effects, at least partly, be obtained via inhibition of the overexpression of integrin β1. These findings suggest that increasing blood flow shear stress properly may serve as a new therapeutic target in reduction of endothelial cell lipid loading and in reversion of endothelial injury by ox- LDL.
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