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- W52413552 abstract "Cyclic mechanical strain produced by pulsatile blood flow regulates the orientation of endothelial cells lining the blood vessels, and influences critical processes such as angiogenesis. Past work has shown that mechanical stimulation of stretch-activated calcium (SAC) channels mediates this reorientation response, however, the molecular basis for this effect remains unknown. Here we show that SAC channels mediate the effects of cyclic strain on endothelial cell reorientation by triggering a signal transduction pathway that controls the activation states of beta 1 integrin and the small GTPase, RhoA. Exposing capillary endothelial cells to uniaxial cyclic strain (10% elongation at 1Hz) caused the cells to realign their focal adhesions, actin stress fibers and longest cell axis perpendicular to the direction of the applied force. Strain application resulted in activation of SAC channel dependent calcium influx within 3 sec followed by activation of PI3-Kinase, beta1 integrin and RhoA. In contrast, strain-induced cytoskeletal reorganization and cell realignment were abolished when SAC channel signaling or activation of either beta 1 integrin or RhoA was inhibited. Importantly, SAC channels acted upstream of beta 1 integrin and Rho, and activation of both signaling molecules was suppressed when SAC channel activity was inhibited. Taken together, these results suggest that cyclic strain induces endothelial cell reorientation by activating calcium influx through SAC channels that, in turn, stimulates PI3K-dependent activation of beta 1 integrins and RhoA." @default.
- W52413552 created "2016-06-24" @default.
- W52413552 creator A5023544944 @default.
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- W52413552 date "2007-01-01" @default.
- W52413552 modified "2023-10-18" @default.
- W52413552 title "Stretch‐activated calcium channels mediate cyclic strain‐induced endothelial cell orientation by controlling activation of beta 1 integrin and RhoA" @default.
- W52413552 doi "https://doi.org/10.1096/fasebj.21.6.lb72" @default.
- W52413552 hasPublicationYear "2007" @default.
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