Piezo1 integration of vascular architecture with physiological force LC-MSMS

ABSTRACT: The mechanisms by which physical forces regulate cells to determine complexities of vascular structure and function are enigmatic. Here we show the role the ion channel subunit Piezo1 (FAM38A). Disruption of mouse Piezo1 gene disturbed vascular development and was embryonic lethal within days of the heart beating to cause blood flow. Importance of Piezo channels as sensors of blood flow was indicated by Piezo1 dependence of shear stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer shear stress sensitivity on cells that otherwise lacked. Downstream of this calcium influx was proteoase activity and spatial organization of endothelial cells to the polarity of the applied force. Without Piezo1, normal endothelial cell organization was lacking. The data suggest Piezo1 channels as pivotal integrators of vascular architacture with physiological mechanical force.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endothelial Cell Of Umbilical Vein, Lung, Lung Cancer Cell Line

DISEASE(S): Arteriosclerotic Cardiovascular Disease

SUBMITTER: David Beech  

LAB HEAD: David J. Beech

PROVIDER: PXD001099 | Pride | 2014-08-08

REPOSITORIES: Pride