Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling.
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The role played by a key protein in the molecular cascade set off by the mechanical strain that blood exerts on vessel walls, which helps strength vessel walls, has been identified.
Since deficiencies in this process can cause atherosclerosis, hypertension and aortic aneurysms, a better knowledge of how cells in the vessel wall respond to physical stimuli could lead to new therapeutic interventions for vascular disease.
A University of Tsukuba–led team focused on a protein called thrombospondin-1 (Thbs1) that is found in the three-dimensional matrix surrounding blood vessels.
They found that rat smooth muscle cells secrete this protein in response to the bulging stretch forces induced by rushing blood flow. Thbs1 then forms complexes with sticky surface proteins on the cells. These anchor points help shuttle another protein, called YAP1, which is needed for stress-associated remodelling of the vessel wall.
Without Thbs1, blood vessels fail to respond properly to mechanical cues and vascular injury, ultimately becoming weakened and dysfunctional.
- PNAS 117, 9896–9905 (2020). doi: 10.1073/pnas.1919702117
|University of Tsukuba, Japan
|Kumamoto University, Japan
|Ibaraki University, Japan