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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2150.)
© 2007 American Heart Association, Inc.

Vascular Biology

Laminar Shear Inhibits Tubule Formation and Migration of Endothelial Cells by an Angiopoietin-2–Dependent Mechanism

Sarah L. Tressel; Ruo-Pan Huang; Nicholas Tomsen; Hanjoong Jo

From the Coulter Department of Biomedical Engineering (S.L.T., H.J.), Georgia Institute of Technology, Department of Gynecology and Obstetrics (R.-P.H.) and Division of Cardiology (H.J.), Emory University, Atlanta, Ga; and the Department of Biological Systems Engineering (N.T.), University of Nebraska, Lincoln.

Correspondence to Hanjoong Jo, Department of Biomedical Engineering, Emory University, WMB 2001, Atlanta, GA 30322. E-mail hanjoong.jo{at}bme.gatech.edu

Objective— 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.

Methods and Results— 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.

Conclusions— 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.

Laminar shear stress promotes endothelial quiescence, whereas oscillatory shear promotes endothelial turnover and dysfunction, which could lead to angiogenesis. We found that Angiopoietin-2 produced by oscillatory shear plays a critical role in migration and tubule formation, which maybe important in diseases with disturbed flow and angiogenesis such as atherosclerosis.

Key Words: shear stress • endothelial cells • angiogenesis • angiopoietin-2

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