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Proteolytic Activity Attenuates the Response of Endothelial Cells to Fluid Shear Stress

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Abstract

Recent evidence indicates that several experimental pathophysiological conditions are associated with elevated protease activity in plasma, which impacts endothelial function. We hypothesize that extracellular structures bound to the endothelial cell (EC) membrane may be degraded by proteolytic activity reducing the cell’s response to physiological shear stress and glucose metabolism efficiency. To test this hypothesis, cultured bovine aortic endothelial cells (BAECs) were exposed to low serine protease activity. Extracellular mechanosensor densities of the glycocalyx and vascular endothelial growth factor receptor 2 (VEGFR-2) were determined. Metabolic dysfunction was tested by examining insulin receptor and glucose uptake levels. Protease treatment impaired the cells’ ability to align in the direction of fluid flow after 12 h of shear stress (12 dyn/cm2); however, cells realigned after an additional 12 h of shear stress with protease inhibition. Proteases caused reduction in the densities of glycocalyx, VEGFR-2, and insulin receptor in static and shear conditions, except for static VEGFR-2 cells. Under static conditions, protease-treated ECs had reduced glucose uptake compared to untreated controls. Under shear, glucose uptake for protease treated BAECs was greater than untreated controls. In conclusion, protease activity in plasma alters the exofacial membrane components of ECs and may interfere with mechanotransduction.

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Acknowledgments

We thank Jerry Norwich for assistance with the confocal microscopy. We also would like to thank Dr. Julie Li and Suli Yuan for valuable discussions. This work was supported by grants HL 10881 and GM-85072 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Bioengineering, The Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, 92093-0412, USA

    Angelina E. Altshuler, Mary J. Morgan, Shu Chien & Geert W. Schmid-Schönbein

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  1. Angelina E. Altshuler
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  2. Mary J. Morgan
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  3. Shu Chien
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  4. Geert W. Schmid-Schönbein
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Correspondence to Angelina E. Altshuler.

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Associate Editor Cheng Dong oversaw the review of this article.

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Altshuler, A.E., Morgan, M.J., Chien, S. et al. Proteolytic Activity Attenuates the Response of Endothelial Cells to Fluid Shear Stress. Cel. Mol. Bioeng. 5, 82–91 (2012). https://doi.org/10.1007/s12195-011-0207-6

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  • DOI: https://doi.org/10.1007/s12195-011-0207-6

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