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Stretch and Shear Interactions Affect Intercellular Junction Protein Expression and Turnover in Endothelial Cells

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Abstract

Complex hemodynamics plays a role in the localization and development of atherosclerosis. Endothelial cells (ECs) lining blood vessel walls are directly influenced by various hemodynamic forces: simultaneous wall shear stress (WSS), normal stress, and circumferential stress/strain (CS) due to pulsatile flow, pressure, and diameter changes. ECs sense and transduce these forces into biomolecular responses that may affect intercellular junctions. In this study, a hemodynamic simulator was used to investigate the combined effects of WSS and CS on EC junctions with emphasis on the stress phase angle (SPA), the temporal phase difference between WSS and CS. Regions of the circulation with highly negative SPA, such as the coronary arteries and carotid bifurcation, are more susceptible to the development of atherosclerosis. At 5 h, expression of the tight junction (TJ) protein zonula occludens-1 was significantly higher for the atheroprotective SPA = 0° compared to the atherogenic SPA = −180° while the apoptosis rate was significantly higher for SPA = −180° than SPA = 0°. This decrease in TJ protein and increase in apoptosis and associated leaky junctions suggest a decreased junctional stability and a higher paracellular permeability for atherogenic macromolecules for the atherogenic SPA = −180° compared to SPA = 0°.

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Acknowledgments

This work was supported by National Institutes of Health National Heart, Lung, and Blood Institute Grants RO1-HL35549 and RO1-HL086543. Thanks to Michael Dancu for help with the dynamic simulator and the supply of tubes.

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Authors and Affiliations

  1. Department of Bioengineering, Pennsylvania State University, University Park, PA, 16802, USA

    Danielle E. Berardi

  2. Department of Biomedical Engineering, City College of New York, Steinman Hall T-401, 140th Street and Convent Avenue, New York, NY, 10031, USA

    Danielle E. Berardi & John M. Tarbell

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Berardi, D.E., Tarbell, J.M. Stretch and Shear Interactions Affect Intercellular Junction Protein Expression and Turnover in Endothelial Cells. Cel. Mol. Bioeng. 2, 320–331 (2009). https://doi.org/10.1007/s12195-009-0073-7

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