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

Nicolas Baeyens (1) , Stefania Nicoli (1) , Brian G. Coon (1) , Tyler D. Ross (1) , Koen van den Dries (1) , Jinah Han (1) , Holly M. Lauridsen (2) , Cécile O. Mejean (1) , Anne Eichmann (1) , Jean-Leon Thomas (3, 4, 5, 6) , Jay D. Humphrey (2) , Martin A. Schwartz (1, 2)

1 YSM - Yale School of Medicine [New Haven, Connecticut]
2 Yale University [New Haven]
3 Department of Neurology
4 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
5 CHU Pitié-Salpêtrière [AP-HP]
6 Le2i - Laboratoire Electronique, Informatique et Image [UMR6306]

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.

Domaines: Biologie cellulaire

Nicolas Baeyens, Stefania Nicoli, Brian G. Coon, Tyler D. Ross, Koen van den Dries, et al.. Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. eLife, 2015, 4, pp.e04645. ⟨10.7554/eLife.04645⟩. ⟨hal-01214976⟩