The analysis of turbulent flow shear stress-responsive genes in vascular endothelial cells

采用DNA微阵列技术对层流或湍流剪切应力作用下的人脐静脉内皮细胞（HUVECs）和冠状动脉内皮细胞（HCAECs）进行基因表达分析。在动脉水平的层流剪切应力（15达因/厘米(2)持续24小时）下，huvec和hcaec中大约3%的5600基因的表达增加了两倍以上，或减少到不到静态对照的一半。在两种细胞系中，在静脉水平的层流剪切应力（1.5 dynes/cm(2)）下，剪切应力响应基因的比例下降到2%左右。1.5 dynes/cm(2)的湍流剪切应力改变了1.1%的hcaec中所有基因的表达。层流剪切应力（而非湍流剪切应力）降低了huvec和hcaec中参与DNA合成和细胞周期的一些基因的表达。聚类分析显示，暴露于15 dynes/cm(2)的层流剪切应力3、6、12、24和48小时后，HUVECs基因表达的时间分布各不相同。湍流剪切应力影响了许多在血管重构中起作用的基因的表达，包括编码纤溶酶原激活剂及其抑制剂、内皮素-1、转化生长因子- β、IV型胶原蛋白和ephrin A1的基因。

DNA microarray gene expression analysis was conducted in human umbilical vein endothelial cells (HUVECs) and coronary artery endothelial cells (HCAECs) exposed to laminar or turbulent shear stress. Approximately 3% of the total 5600 gene in HUVECs and HCAECs increased their expression more than two-fold or decreased it to less than half the static control in response to an arterial level of laminar shear stress (15 dynes/cm(2) for 24 hours). The proportions of shear-stress-responsive genes decreased to around 2% under the venous level of laminar shear stress (1.5 dynes/cm(2)) in both cell lines. Turbulent shear stress of 1.5 dynes/cm(2) altered the expression of 1.1% of all genes in the HCAECs. Laminar shear stress, but not turbulent shear stress, decreased the expression of a number of genes involved in DNA synthesis and the cell cycle in both HUVECs and HCAECs. Clustering analysis showed a variety of temporal profiles of gene expression in HUVECs exposed to laminar shear stress of 15 dynes/cm(2) for 3, 6, 12, 24, and 48 hours. Turbulent shear stress affected expression of many genes that play a role in vascular remodeling, including genes encoding plasminogen activators and their inhibitor, endothelin-1, transforming growth factor-beta, collagen type IV, and ephrin A1.