on March 29, 2007
Published online before print March 29, 2007, doi: 10.1161/ATVBAHA.107.142778
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 3, 2006
Accepted on March 19, 2007
Cyclic Strain Regulates the Notch/CBF-1 Signaling Pathway in Endothelial Cells. Role in Angiogenic Activity
David Morrow ;
From the Department of Surgery (D.M., J.P.C., E.M.R.), University of Rochester Medical Center, Rochester, NY; and the Vascular Health Research Centre (P.A.C.), Dublin City University, Dublin, Ireland.
* To whom correspondence should be addressed. E-mail: Eileen_Redmond{at}urmc.rochester.edu.
Objective--The purpose of this study was to determine the effect of cyclic strain on Notch signaling in endothelial cells.
Methods and Results--Exposure of human endothelial cells (ECs) to cyclic strain (10%) resulted in temporal upregulation of Notch receptors (1 and 4) at the mRNA and protein level. Cyclic strain significantly increased EC network formation on Matrigel (an index of angiogenesis); network AU=775±127 versus 3928±400 for static and strained ECs, respectively. In addition, Angiopoietin 1 (Ang1), Tie1, and Tie2 expression were increased and knockdown of Ang1/Tie1,2 by siRNAs decreased cyclic strain-induced network formation. Knockdown of Notch 1 and 4 by siRNA, or inhibition of Notch mediated CBF-1/RBP-Jk regulated gene expression by RPMS-1, caused a significant decrease in cyclic strain-induced network formation and in Tie1 and Tie2 mRNA expression. Notch 1 or Notch 4 siRNA, but not RPMS-1, inhibited cyclic strain-induced Ang1. Constitutive overexpression of Notch IC resulted in increased network formation, and Ang1 and Tie2 mRNA expression, under both static and strain conditions.
Conclusions--These data suggest that cyclic strain-stimulated EC angiogenesis is mediated in part through a Notch-dependent, Ang1/Tie2 signaling pathway. This pathway may represent a novel therapeutic target for disease states in which hemodynamic force-induced angiogenesis occurs.
Key words: mechanical forces • Notch • endothelial cells • angiogenesis • angiopoietin
This article has been cited by other articles:
 |
|
 |
|
  D. Morrow, J. P. Cullen, W. Liu, S. Guha, C. Sweeney, Y. A. Birney, N. Collins, D. Walls, E. M. Redmond, and P. A. Cahill Sonic Hedgehog Induces Notch Target Gene Expression in Vascular Smooth Muscle Cells via VEGF-A Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 1112 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zheng, L. P. Christensen, and R. J. Tomanek Differential effects of cyclic and static stretch on coronary microvascular endothelial cell receptors and vasculogenic/angiogenic responses Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H794 - H800. [Abstract] [Full Text] [PDF]
|
|