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.
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.
Authors: Nolan L Boyd; Heonyong Park; Hong Yi; Yong Chool Boo; George P Sorescu; Michelle Sykes; Hanjoong Jo Journal: Am J Physiol Heart Circ Physiol Date: 2003-05-22 Impact factor: 4.733
Authors: Nicholas W Gale; Gavin Thurston; Sean F Hackett; Roumiana Renard; Quan Wang; Joyce McClain; Cliff Martin; Charles Witte; Marlys H Witte; David Jackson; Chitra Suri; Peter A Campochiaro; Stanley J Wiegand; George D Yancopoulos Journal: Dev Cell Date: 2002-09 Impact factor: 12.270
Authors: Cristina Calvi; Patrizia Dentelli; Marco Pagano; Arturo Rosso; Marco Pegoraro; Sara Giunti; Giovanni Garbarino; Giovanni Camussi; Luigi Pegoraro; Maria Felice Brizzi Journal: Arterioscler Thromb Vasc Biol Date: 2004-01-15 Impact factor: 8.311
Authors: George P Sorescu; Michelle Sykes; Daiana Weiss; Manu O Platt; Aniket Saha; Jinah Hwang; Nolan Boyd; Yong C Boo; J David Vega; W Robert Taylor; Hanjoong Jo Journal: J Biol Chem Date: 2003-05-23 Impact factor: 5.157
Authors: Jing Tian; Sohrab Fratz; Yali Hou; Qing Lu; Agnes Görlach; John Hess; Christian Schreiber; Sanjeev A Datar; Peter Oishi; John Nechtman; Robert Podolsky; Jin-Xiong She; Jeffrey R Fineman; Stephen M Black Journal: Physiol Genomics Date: 2010-10-26 Impact factor: 3.107
Authors: Christine M Gross; Saurabh Aggarwal; Sanjiv Kumar; Jing Tian; Anita Kasa; Natalia Bogatcheva; Sanjeev A Datar; Alexander D Verin; Jeffrey R Fineman; Stephen M Black Journal: J Cell Physiol Date: 2014-11 Impact factor: 6.384
Authors: Sara S Nunes; Kevin A Greer; Chad M Stiening; Helen Y S Chen; Kameha R Kidd; Mark A Schwartz; Chris J Sullivan; Harish Rekapally; James B Hoying Journal: Microvasc Res Date: 2009-10-13 Impact factor: 3.514