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Publication : Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point.

First Author  Baeyens N Year  2015
Journal  Elife Volume  4
PubMed ID  25643397 Mgi Jnum  J:269461
Mgi Id  MGI:6204125 Doi  10.7554/eLife.04645
Citation  Baeyens N, et al. (2015) Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. Elife 4
abstractText  Vascular remodeling under conditions of growth or exercise, or during recovery from arterial restriction or blockage is essential for health, but mechanisms are poorly understood. It has been proposed that endothelial cells have a preferred level of fluid shear stress, or 'set point', that determines remodeling. We show that human umbilical vein endothelial cells respond optimally within a range of fluid shear stress that approximate physiological shear. Lymphatic endothelial cells, which experience much lower flow in vivo, show similar effects but at lower value of shear stress. VEGFR3 levels, a component of a junctional mechanosensory complex, mediate these differences. Experiments in mice and zebrafish demonstrate that changing levels of VEGFR3/Flt4 modulates aortic lumen diameter consistent with flow-dependent remodeling. These data provide direct evidence for a fluid shear stress set point, identify a mechanism for varying the set point, and demonstrate its relevance to vessel remodeling in vivo.
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