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Glycated Collagen Impairs Endothelial Cell Response to Cyclic Stretch

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Abstract

People with diabetes suffer from accelerated, diffuse atherosclerosis. Endothelial cells are dysfunctional in high glucose and on glycated collagen, but their response to mechanical stimuli in a high glucose environment has not been examined. The aim of this study was to determine the effect of glycated collagen on aortic endothelial cell response to strain. Porcine aortic endothelial cells seeded on either native or glycated collagen coated elastic substrates were exposed to 10% cyclic strain. While cells on native collagen aligned and formed actin stress fibers perpendicular to the stretch direction after 6 h, cells on glycated collagen did not align even after 12 h of cyclic strain. Impaired actin alignment could be related to diminished focal adhesion kinase phosphorylation in cells on glycated collagen. We further show that loss of mechanotransduction affects endothelial cell barrier function. Cells on glycated collagen substrates demonstrated a threefold increase in permeability with strain, whereas cell permeability on native collagen was unchanged. Increased permeability could be related to altered cell–cell junction morphology, as evidenced by β-catenin immunofluorescence. We hypothesize that impaired endothelial cell mechanotransduction on glycated collagen is due to altered integrin interactions. These data suggest that endothelial cells exposed to diabetic hyperglycemia are unable to adapt to the mechanical environment and thereby continue to express a pro-atherosclerotic phenotype.

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Acknowledgments

This research was funded by NSF CAREER award (CBET-0846751) and AHA Scientist Development Grant to Alisa Morss Clyne; UNCF-Merck Graduate Science Research Dissertation Fellowship, NSF IGERT fellowship (DGE-0654313), and NSF Bridge to the Doctorate fellowship to Dannielle S. Figueroa; and NSF GK-12 fellowship and Department of Education GAANN fellowship to Steven Kemeny. The authors would like to thank summer research assistants Heather Weber and Manjima Dhar for their contributions to the project.

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  1. School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA

    Dannielle Solomon Figueroa

  2. Department of Mechanical Engineering and Mechanics, Drexel University, 3141 Chestnut Street, 170C Alumni Labs, Philadelphia, PA, 19104, USA

    Steven Frank Kemeny & Alisa Morss Clyne

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  1. Dannielle Solomon Figueroa
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Correspondence to Alisa Morss Clyne.

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Associate Editors Yingxiao Wang & Peter J. Butler oversaw the review of this article.

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Figueroa, D.S., Kemeny, S.F. & Clyne, A.M. Glycated Collagen Impairs Endothelial Cell Response to Cyclic Stretch. Cel. Mol. Bioeng. 4, 220–230 (2011). https://doi.org/10.1007/s12195-011-0176-9

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