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Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation
Journal article   Open access   Peer reviewed

Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation

Rebecca Lownes Urbano, Swathi Swaminathan and Alisa Morss Clyne
Applied bionics and biomechanics, v 2019, pp 6578492-14
01 Jan 2019
PMID: 31110559
url
https://doi.org/10.1155/2019/6578492View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

Engineering Engineering, Biomedical Robotics Science & Technology Technology
Arterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The objective of this study was to determine if substrate stiffness increased endothelial monolayer reactive oxygen species (ROS) in response to protein kinase C (PKC) activation and if this oxidative stress then impacted adherens junction integrity. Porcine aortic endothelial cells were cultured on varied stiffness polyacrylamide gels and treated with phorbol 12-myristate 13-acetate (PMA), which stimulates PKC and ROS without increasing actinomyosin contractility. PMA-treated endothelial cells on stiffer substrates increased ROS and adherens junction loss without increased contractility. ROS scavengers abrogated PMA effects on cell-cell junctions, with a more profound effect in cells on stiffer substrates. Finally, endothelial cells in aortae from elastin haploinsufficient mice (Eln+/-), which were stiffer than aortae from wild-type mice, showed decreased VE-cadherin colocalization with peripheral actin following PMA treatment. These data suggest that oxidative stress may be enhanced in endothelial cells in stiffer vessels, which could contribute to the association between arterial stiffness and cardiovascular disease.

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Web of Science research areas
Engineering, Biomedical
Robotics
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