Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells

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Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells. / Chuang, Christine Y; Degendorfer, Georg; Hammer, Astrid; Whitelock, John M; Malle, Ernst; Davies, Michael Jonathan.

In: Biochemical Journal, Vol. 459, No. 2, 15.04.2014, p. 313-22.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Chuang, CY, Degendorfer, G, Hammer, A, Whitelock, JM, Malle, E & Davies, MJ 2014, 'Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells', Biochemical Journal, vol. 459, no. 2, pp. 313-22. https://doi.org/10.1042/BJ20131471

APA

Chuang, C. Y., Degendorfer, G., Hammer, A., Whitelock, J. M., Malle, E., & Davies, M. J. (2014). Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells. Biochemical Journal, 459(2), 313-22. https://doi.org/10.1042/BJ20131471

Vancouver

Chuang CY, Degendorfer G, Hammer A, Whitelock JM, Malle E, Davies MJ. Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells. Biochemical Journal. 2014 Apr 15;459(2):313-22. https://doi.org/10.1042/BJ20131471

Author

Chuang, Christine Y ; Degendorfer, Georg ; Hammer, Astrid ; Whitelock, John M ; Malle, Ernst ; Davies, Michael Jonathan. / Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells. In: Biochemical Journal. 2014 ; Vol. 459, No. 2. pp. 313-22.

Bibtex

@article{cb94cacf176a40d08b6753463b801439,
title = "Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells",
abstract = "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.",
keywords = "Atherosclerosis, Cells, Cultured, Coronary Vessels, Endothelial Cells, Extracellular Matrix Proteins, Gene Expression Regulation, Humans, Oxidants, Oxidation-Reduction, Peroxynitrous Acid",
author = "Chuang, {Christine Y} and Georg Degendorfer and Astrid Hammer and Whitelock, {John M} and Ernst Malle and Davies, {Michael Jonathan}",
year = "2014",
month = "4",
day = "15",
doi = "10.1042/BJ20131471",
language = "English",
volume = "459",
pages = "313--22",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "2",

}

RIS

TY - JOUR

T1 - Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells

AU - Chuang, Christine Y

AU - Degendorfer, Georg

AU - Hammer, Astrid

AU - Whitelock, John M

AU - Malle, Ernst

AU - Davies, Michael Jonathan

PY - 2014/4/15

Y1 - 2014/4/15

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Cells, Cultured

KW - Coronary Vessels

KW - Endothelial Cells

KW - Extracellular Matrix Proteins

KW - Gene Expression Regulation

KW - Humans

KW - Oxidants

KW - Oxidation-Reduction

KW - Peroxynitrous Acid

U2 - 10.1042/BJ20131471

DO - 10.1042/BJ20131471

M3 - Journal article

C2 - 24517414

VL - 459

SP - 313

EP - 322

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -

ID: 128973816