ECM (extracellular matrix) materials, such as laminin, perlecan, type IV collagen and fibronectin, play a key role in determining the structure of the arterial wall and the properties of cells that interact with the ECM. The aim of the present study was to investigate the effect of peroxynitrous acid, an oxidant generated by activated macrophages, on the structure and function of the ECM laid down by HCAECs (human coronary artery endothelial cells) in vitro and in vivo. We show that exposure of HCAEC-derived native matrix components to peroxynitrous acid (but not decomposed oxidant) at concentrations >1 μM results in a loss of antibody recognition of perlecan, collagen IV, and cell-binding sites on laminin and fibronectin. Loss of recognition was accompanied by decreased HCAEC adhesion. Real-time PCR showed up-regulation of inflammation-associated genes, including MMP7 (matrix metalloproteinase 7) and MMP13, as well as down-regulation of the laminin α2 chain, in HCAECs cultured on peroxynitrous acid-treated matrix compared with native matrix. Immunohistochemical studies provided evidence of co-localization of laminin with 3-nitrotyrosine, a biomarker of peroxynitrous acid damage, in type II–III/IV human atherosclerotic lesions, consistent with matrix damage occurring during disease development in vivo. The results of the present study suggest a mechanism through which peroxynitrous acid modifies endothelial cell-derived native ECM proteins of the arterial basement membrane in atherosclerotic lesions. These changes to ECM and particularly perlecan and laminin may be important in inducing cellular dysfunction and contribute to atherogenesis.
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Research Article|
March 28 2014
Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells Available to Purchase
Christine Y. Chuang;
Christine Y. Chuang
*The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia
†Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia
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Georg Degendorfer;
Georg Degendorfer
*The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia
†Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia
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Astrid Hammer;
Astrid Hammer
‡Institute of Cell Biology, Histology and Embryology, Center for Molecular Medicine, Medical University of Graz, Graz, Austria
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John M. Whitelock;
John M. Whitelock
§Graduate School of Biomedical Engineering, The University of New South Wales, Kensington, NSW, Australia
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Ernst Malle;
Ernst Malle
¶Institute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Graz, Austria
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Michael J. Davies
Michael J. Davies
1
*The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia
†Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
November 06 2013
Revision Received:
February 10 2014
Accepted:
February 12 2014
Accepted Manuscript online:
February 12 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 459 (2): 313–322.
Article history
Received:
November 06 2013
Revision Received:
February 10 2014
Accepted:
February 12 2014
Accepted Manuscript online:
February 12 2014
Citation
Christine Y. Chuang, Georg Degendorfer, Astrid Hammer, John M. Whitelock, Ernst Malle, Michael J. Davies; Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells. Biochem J 15 April 2014; 459 (2): 313–322. doi: https://doi.org/10.1042/BJ20131471
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