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

用DNA微阵列技术分析了层流和湍流剪切力作用下的人脐静脉内皮细胞和冠状动脉内皮细胞的基因表达。在HUVECs和HCAECs中，大约3%的5600基因的表达水平在动脉层流切应力(15dynes/cm(2)持续24小时)下增加了两倍以上，或降低到不到静态对照的一半。在静脉水平的层流切应力(1.5dynes/cm(2))下，两种细胞系中剪应力反应基因的比例都下降到2%左右。1.5dynes/cm(2)的湍流剪切力改变了HCAEC中1.1%的基因表达。层流切应力，而不是湍流切应力，降低了HUVECs和HCAECs中与DNA合成和细胞周期有关的一些基因的表达。聚类分析显示，HUVEC暴露在15dynes/cm(2)的层流切应力作用3、6、12、24和48小时后，基因表达的时间分布各不相同。湍流切应力影响了许多在血管重塑中起作用的基因的表达，包括编码纤溶酶原激活物及其抑制物、内皮素-1、转化生长因子-β、IV型胶原和肾上腺素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.