PUBLICATION
Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point
- Authors
- Baeyens, N., Nicoli, S., Coon, B.G., Ross, T.D., Van den Dries, K., Han, J., Lauridsen, H.M., Mejean, C.O., Eichmann, A., Thomas, J.L., Humphrey, J.D., Schwartz, M.A.
- ID
- ZDB-PUB-150203-1
- Date
- 2015
- Source
- eLIFE 4: (Journal)
- Registered Authors
- Keywords
- arteriogenesis, cell biology, homeostasis, human, human biology, mechanotransduction, medicine, mouse, shear stress, vascular remodeling, zebrafish
- MeSH Terms
-
- Animals
- Endothelium, Vascular/physiology
- Human Umbilical Vein Endothelial Cells
- Humans
- Mice
- Stress, Physiological*
- Umbilical Veins/physiology*
- Vascular Endothelial Growth Factor Receptor-3/physiology*
- Vascular Remodeling*
- Zebrafish
- PubMed
- 25643397 Full text @ Elife
Citation
Baeyens, N., Nicoli, S., Coon, B.G., Ross, T.D., Van den Dries, K., Han, J., Lauridsen, H.M., Mejean, C.O., Eichmann, A., Thomas, J.L., Humphrey, J.D., Schwartz, M.A. (2015) Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. eLIFE. 4.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping