Blood vessel size control

Blood vessel size control

Many vascular structures are organized in a hierarchical pattern, resembling trees. This organization is important for the efficient distribution of blood throughout the body. We are studying how blood vessels know which size they should have in order to properly built such trees. We identified a zebrafish homologue for endoglin, a gene that causes hereditary hemorrhagic telangiectasia (HHT), a vascular disease in humans. In the zebrafish mutants for this gene, blood vessels are too big, leading to aberrantly patterned vascular trees. We also found that the size of a given blood vessel is dependent on the shapes of the cells building this blood vessel and that cells in endoglin mutants failed to obtain their proper shapes. We could also determine that cells change their shapes in response to changes in the magnitude of blood flow they experience. Current research aims at understanding how endoglin might influence cell shapes and which mechanisms allow endothelial cells to properly respond to changes in blood flow.

We also found that cells ensheathing vascular endothelial cells, so called mural cells, play an important role in controlling blood vessel sizes. In order to study these cells, we have generated several transgenic lines, in which mural cells were engineered to express fluorescent proteins, allowing for detailed imaging of their interactions with endothelial cells. How mural cells might influence endothelial cell shapes and blood vessel sizes is an important research question in the laboratory.

Publications

Sugden W.W., Siekmann A.F. (2018). Endothelial cell biology of Endoglin in Hereditary Hemorrhagic Telangiectasia.Current Opinion in Hematology, May;25(3):237-244.

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):653-65.