PUBLICATION
Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues
- Authors
- Sugden, W.W., Meissner, R., Aegerter-Wilmsen, T., Tsaryk, R., Leonard, E.V., Bussmann, J., Hamm, M.J., Herzog, W., Jin, Y., Jakobsson, L., Denz, C., Siekmann, A.F.
- ID
- ZDB-PUB-170523-5
- Date
- 2017
- Source
- Nature cell biology 19(6): 653-665 (Journal)
- Registered Authors
- Bussmann, Jeroen, Herzog, Wiebke, Siekmann, Arndt Friedrich
- Keywords
- none
- MeSH Terms
-
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Cell Shape*
- Endothelial Cells/metabolism*
- Endoglin/deficiency
- Endoglin/genetics
- Endoglin/metabolism*
- Regional Blood Flow
- Neovascularization, Physiologic
- Human Umbilical Vein Endothelial Cells/metabolism
- Mutation
- Genetic Predisposition to Disease
- Kruppel-Like Transcription Factors/genetics
- Kruppel-Like Transcription Factors/metabolism
- Hemodynamics*
- Humans
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Arteriovenous Malformations/genetics
- Arteriovenous Malformations/metabolism
- Arteriovenous Malformations/physiopathology
- Animals
- Stress, Mechanical
- Time Factors
- Mice, Knockout
- Mechanotransduction, Cellular*
- Phenotype
- PubMed
- 28530658 Full text @ Nat. Cell Biol.
Citation
Sugden, W.W., Meissner, R., Aegerter-Wilmsen, T., Tsaryk, R., Leonard, E.V., Bussmann, J., Hamm, M.J., Herzog, W., Jin, Y., Jakobsson, L., Denz, C., Siekmann, A.F. (2017) Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues. Nature cell biology. 19(6):653-665.
Abstract
The hierarchical organization of properly sized blood vessels ensures the correct distribution of blood to all organs of the body, and is controlled via haemodynamic cues. In current concepts, an endothelium-dependent shear stress set point causes blood vessel enlargement in response to higher flow rates, while lower flow would lead to blood vessel narrowing, thereby establishing homeostasis. We show that during zebrafish embryonic development increases in flow, after an initial expansion of blood vessel diameters, eventually lead to vessel contraction. This is mediated via endothelial cell shape changes. We identify the transforming growth factor beta co-receptor endoglin as an important player in this process. Endoglin mutant cells and blood vessels continue to enlarge in response to flow increases, thus exacerbating pre-existing embryonic arterial-venous shunts. Together, our data suggest that cell shape changes in response to biophysical cues act as an underlying principle allowing for the ordered patterning of tubular organs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping