Tressel Sarah L, Huang Ruo-Pan, Tomsen Nicholas, Jo Hanjoong
Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2150-6. doi: 10.1161/ATVBAHA.107.150920. Epub 2007 Aug 2.
Fluid shear stress plays a role in angiogenesis. Laminar shear stress (LS) promotes endothelial cell (EC) quiescence, whereas oscillatory shear stress (OS) promotes EC turnover and dysfunction, which could lead to pathological angiogenesis. We hypothesized that LS inhibits EC migration and tubule formation, 2 functions important in angiogenesis, by inhibiting the secretion of proangiogenic factors.
Human umbilical vein ECs (HUVECs), human microvascular ECs (HMECs), or bovine aortic ECs (BAECs) were subjected to either LS (15 dyn/cm2) or OS (+/-5 dyn/cm2) for 24 hours and used in Matrigel tubule formation or scratch migration assays. Exposure of HUVECs, HMECs, but not BAECs, to LS inhibited tubule formation compared with OS. LS also inhibited migration of HUVECs and BAECs compared with OS. Angiopoietin-2 (Ang2), a known angiogenic protein, was found to be downregulated by LS both in cultured ECs and mouse aortas. Using Ang2 siRNA, Ang2 knockdown blocked OS-mediated migration and tubule formation and the LS-inhibited tubule formation was partially rescued by recombinant Ang2.
Our data suggests that Ang2 produced by OS in ECs plays a critical role in migration and tubule formation, and may play an important role in diseases with disturbed flow and angiogenesis.
流体剪切应力在血管生成中起作用。层流剪切应力（LS）促进内皮细胞（EC）静止，而振荡剪切应力（OS）促进EC更新和功能障碍，这可能导致病理性血管生成。我们假设LS通过抑制促血管生成因子的分泌来抑制EC迁移和小管形成，这是血管生成中的两个重要功能。
将人脐静脉内皮细胞（HUVECs）、人微血管内皮细胞（HMECs）或牛主动脉内皮细胞（BAECs）分别置于LS（15达因/平方厘米）或OS（±5达因/平方厘米）下24小时，并用于基质胶小管形成或划痕迁移试验。与OS相比，将HUVECs、HMECs而非BAECs暴露于LS可抑制小管形成。与OS相比，LS也抑制HUVECs和BAECs的迁移。血管生成素-2（Ang2）是一种已知的血管生成蛋白，发现在培养的内皮细胞和小鼠主动脉中均被LS下调。使用Ang2小干扰RNA（siRNA），敲低Ang2可阻断OS介导的迁移和小管形成，并且重组Ang2可部分挽救LS抑制的小管形成。
我们的数据表明，EC中由OS产生的Ang2在迁移和小管形成中起关键作用，并且可能在血流紊乱和血管生成异常的疾病中起重要作用。
