Hypochlorous acid-modified extracellular matrix contributes to the behavioral switching of human coronary artery smooth muscle cells

Huan Cai; Christine Y. Chuang; Siriluck Vanichkitrungruang; Clare L. Hawkins; Michael J. Davies

doi:10.1016/j.freeradbiomed.2019.01.044

Hypochlorous acid-modified extracellular matrix contributes to the behavioral switching of human coronary artery smooth muscle cells

Huan Cai, Christine Y. Chuang, Siriluck Vanichkitrungruang, Clare L. Hawkins, Michael J. Davies

Inflammation, Metabolism and Oxidation

13 Citations (Scopus)

Abstract

The extracellular matrix (ECM) influences the structure and function of the arterial wall and modulates the behavior of vascular cells through ECM-cell interactions. Alterations to the ECM have been implicated in multiple pathological processes, including atherosclerosis which is characterized by low-grade chronic inflammation and the infiltration and proliferation of smooth muscle cells during disease development. Considerable evidence has been presented for a role for inflammation-derived oxidation in atherogenesis, with enzymatically-active myeloperoxidase (MPO), elevated levels of 3-chlorotyrosine (a biomarker of MPO-catalyzed damage) and oxidized ECM materials detected in advanced human atherosclerotic lesions. Whether oxidant-modified ECM contributes to the altered behavior of smooth muscle cells is however unclear. This study therefore investigated the effects of hypochlorous acid (HOCl), a major MPO-derived oxidant, on the structure of the native ECM synthesized by human coronary artery smooth muscle cells (HCAMSCs) and whether modified ECM proteins affected HCASMC adhesion, proliferation and gene expression. Exposure of native HCASMC-derived ECM to reagent HOCl or a MPO-Cl--H2O2 system resulted in extensive ECM modifications as evidenced by the loss of antibody recognition of epitopes on type IV collagen, laminin, versican and fibronectin. Oxidation of HCASMC ECM markedly reduced HCASMC adhesion to matrix components, but facilitated subsequent proliferation in vitro. Multiple genes were upregulated in HCASMCs in response to HOCl-modified HCASMC-ECM including interleukin-6 (IL-6), fibronectin (FN1) and matrix-metalloproteinases (MMPs). These data reveal a mechanism through which inflammation-induced ECM-modification may contribute to the behavioral switching of HCASMCs, a key process in plaque formation during the development of atherosclerosis.

Original language	English
Journal	Free Radical Biology and Medicine
Volume	134
Pages (from-to)	526-536
ISSN	0891-5849
DOIs	https://doi.org/10.1016/j.freeradbiomed.2019.01.044
Publication status	Published - Apr 2019

Keywords

Hypochlorous acid
Extracellular matrix
Human coronary artery smooth muscle cells
Myeloperoxidase
Protein oxidation
Atherosclerosis

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10.1016/j.freeradbiomed.2019.01.044

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@article{64362982f2654c059c4af6d107bcbb20,

title = "Hypochlorous acid-modified extracellular matrix contributes to the behavioral switching of human coronary artery smooth muscle cells",

abstract = "The extracellular matrix (ECM) influences the structure and function of the arterial wall and modulates the behavior of vascular cells through ECM-cell interactions. Alterations to the ECM have been implicated in multiple pathological processes, including atherosclerosis which is characterized by low-grade chronic inflammation and the infiltration and proliferation of smooth muscle cells during disease development. Considerable evidence has been presented for a role for inflammation-derived oxidation in atherogenesis, with enzymatically-active myeloperoxidase (MPO), elevated levels of 3-chlorotyrosine (a biomarker of MPO-catalyzed damage) and oxidized ECM materials detected in advanced human atherosclerotic lesions. Whether oxidant-modified ECM contributes to the altered behavior of smooth muscle cells is however unclear. This study therefore investigated the effects of hypochlorous acid (HOCl), a major MPO-derived oxidant, on the structure of the native ECM synthesized by human coronary artery smooth muscle cells (HCAMSCs) and whether modified ECM proteins affected HCASMC adhesion, proliferation and gene expression. Exposure of native HCASMC-derived ECM to reagent HOCl or a MPO-Cl--H2O2 system resulted in extensive ECM modifications as evidenced by the loss of antibody recognition of epitopes on type IV collagen, laminin, versican and fibronectin. Oxidation of HCASMC ECM markedly reduced HCASMC adhesion to matrix components, but facilitated subsequent proliferation in vitro. Multiple genes were upregulated in HCASMCs in response to HOCl-modified HCASMC-ECM including interleukin-6 (IL-6), fibronectin (FN1) and matrix-metalloproteinases (MMPs). These data reveal a mechanism through which inflammation-induced ECM-modification may contribute to the behavioral switching of HCASMCs, a key process in plaque formation during the development of atherosclerosis.",

keywords = "Hypochlorous acid, Extracellular matrix, Human coronary artery smooth muscle cells, Myeloperoxidase, Protein oxidation, Atherosclerosis",

author = "Huan Cai and Chuang, {Christine Y.} and Siriluck Vanichkitrungruang and Hawkins, {Clare L.} and Davies, {Michael J.}",

year = "2019",

month = apr,

doi = "10.1016/j.freeradbiomed.2019.01.044",

language = "English",

volume = "134",

pages = "526--536",

journal = "Free Radical Biology and Medicine",

issn = "0891-5849",

publisher = "Elsevier",

}

TY - JOUR

T1 - Hypochlorous acid-modified extracellular matrix contributes to the behavioral switching of human coronary artery smooth muscle cells

AU - Cai, Huan

AU - Chuang, Christine Y.

AU - Vanichkitrungruang, Siriluck

AU - Hawkins, Clare L.

AU - Davies, Michael J.

PY - 2019/4

Y1 - 2019/4

N2 - The extracellular matrix (ECM) influences the structure and function of the arterial wall and modulates the behavior of vascular cells through ECM-cell interactions. Alterations to the ECM have been implicated in multiple pathological processes, including atherosclerosis which is characterized by low-grade chronic inflammation and the infiltration and proliferation of smooth muscle cells during disease development. Considerable evidence has been presented for a role for inflammation-derived oxidation in atherogenesis, with enzymatically-active myeloperoxidase (MPO), elevated levels of 3-chlorotyrosine (a biomarker of MPO-catalyzed damage) and oxidized ECM materials detected in advanced human atherosclerotic lesions. Whether oxidant-modified ECM contributes to the altered behavior of smooth muscle cells is however unclear. This study therefore investigated the effects of hypochlorous acid (HOCl), a major MPO-derived oxidant, on the structure of the native ECM synthesized by human coronary artery smooth muscle cells (HCAMSCs) and whether modified ECM proteins affected HCASMC adhesion, proliferation and gene expression. Exposure of native HCASMC-derived ECM to reagent HOCl or a MPO-Cl--H2O2 system resulted in extensive ECM modifications as evidenced by the loss of antibody recognition of epitopes on type IV collagen, laminin, versican and fibronectin. Oxidation of HCASMC ECM markedly reduced HCASMC adhesion to matrix components, but facilitated subsequent proliferation in vitro. Multiple genes were upregulated in HCASMCs in response to HOCl-modified HCASMC-ECM including interleukin-6 (IL-6), fibronectin (FN1) and matrix-metalloproteinases (MMPs). These data reveal a mechanism through which inflammation-induced ECM-modification may contribute to the behavioral switching of HCASMCs, a key process in plaque formation during the development of atherosclerosis.

AB - The extracellular matrix (ECM) influences the structure and function of the arterial wall and modulates the behavior of vascular cells through ECM-cell interactions. Alterations to the ECM have been implicated in multiple pathological processes, including atherosclerosis which is characterized by low-grade chronic inflammation and the infiltration and proliferation of smooth muscle cells during disease development. Considerable evidence has been presented for a role for inflammation-derived oxidation in atherogenesis, with enzymatically-active myeloperoxidase (MPO), elevated levels of 3-chlorotyrosine (a biomarker of MPO-catalyzed damage) and oxidized ECM materials detected in advanced human atherosclerotic lesions. Whether oxidant-modified ECM contributes to the altered behavior of smooth muscle cells is however unclear. This study therefore investigated the effects of hypochlorous acid (HOCl), a major MPO-derived oxidant, on the structure of the native ECM synthesized by human coronary artery smooth muscle cells (HCAMSCs) and whether modified ECM proteins affected HCASMC adhesion, proliferation and gene expression. Exposure of native HCASMC-derived ECM to reagent HOCl or a MPO-Cl--H2O2 system resulted in extensive ECM modifications as evidenced by the loss of antibody recognition of epitopes on type IV collagen, laminin, versican and fibronectin. Oxidation of HCASMC ECM markedly reduced HCASMC adhesion to matrix components, but facilitated subsequent proliferation in vitro. Multiple genes were upregulated in HCASMCs in response to HOCl-modified HCASMC-ECM including interleukin-6 (IL-6), fibronectin (FN1) and matrix-metalloproteinases (MMPs). These data reveal a mechanism through which inflammation-induced ECM-modification may contribute to the behavioral switching of HCASMCs, a key process in plaque formation during the development of atherosclerosis.

KW - Hypochlorous acid

KW - Extracellular matrix

KW - Human coronary artery smooth muscle cells

KW - Myeloperoxidase

KW - Protein oxidation

KW - Atherosclerosis

U2 - 10.1016/j.freeradbiomed.2019.01.044

DO - 10.1016/j.freeradbiomed.2019.01.044

M3 - Journal article

C2 - 30716431

SN - 0891-5849

VL - 134

SP - 526

EP - 536

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -