A Bio-Engineering Approach to Endothelial Cell Signal Transduction and Responses to Fluid Shear Stress

点击翻译按钮获取中文摘要

We applied controlled levels of fluid shear stress to cultured endothelial cells (ECs) in a specially designed flow-loading chamber, and examined the changes in intracellular Ca^<2+> concentrations ([Ca^<2+>]) and adhesion molecule expressions.When subjected to shear stress in the presence of extracellular ATP,ECs showed the increase in [Ca^<2+>]. Different patterns including peak & plateau, oscillation, and transient were observed in individual cells. The percentage of the pattern was 62%, 32%and6%, respectively. Regardless of the patterns, [Ca^<2+>] increase initiated from specific loci at cell edges, and propagated through the entire cell body as a Ca^<2+> wave. The loci corresponded to the caveolin-rich in ECs, suggesting that the information of shear stress enters via caveolae.Shear stress inhibited the cell surface expression of vascular adhesion molecule-1 (VCAM-1) in mouse lymphnode venule ECs, and simultaneously decreased the mRNA levels. The decrease in mRNA levels was due to the suppression of VCAM-1 gene transcription, and double AP1 consensus elements in VCAM-1 promoter was essential for the shear-induced suppression of transcriptional activity. This is a negative shear stress responsive element, which was first demonstrated by this study.