Binding of myeloperoxidase to the extracellular matrix of smooth muscle cells and subsequent matrix modification.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Extracellular Matrix/*metabolism ; Extracellular Matrix/*pathology ; Hypochlorous Acid/*metabolism ; Myocytes, Smooth Muscle/*metabolism ; Peroxidase/*adverse effects ; Peroxidase/*metabolism; Antibody Formation ; Cell Adhesion ; Cell Proliferation ; Cells, Cultured ; Collagen/immunology ; Extracellular Matrix/immunology ; Extracellular Matrix Proteins/metabolism ; Fibronectins/immunology ; Gene Expression ; Humans ; Hypochlorous Acid/adverse effects ; Myocytes, Smooth Muscle/physiology ; Protein Binding ; Versicans/immunology

The extracellular matrix (ECM) of tissues is susceptible to modification by inflammation-associated oxidants. Considerable data support a role for hypochlorous acid (HOCl), generated by the leukocyte-derived heme-protein myeloperoxidase (MPO) in these changes. HOCl can modify isolated ECM proteins and cell-derived matrix, with this resulting in decreased cell adhesion, modulated proliferation and gene expression, and phenotypic changes. Whether this arises from free HOCl, or via site-specific reactions is unresolved. Here we examine the mechanisms of MPO-mediated changes to human coronary smooth muscle cell ECM. MPO is shown to co-localize with matrix fibronectin as detected by confocal microscopy, and bound active MPO can initiate ECM modification, as detected by decreased antibody recognition of fibronectin, versican and type IV collagen, and formation of protein carbonyls and HOCl-mediated damage. These changes are recapitulated by a glucose/glucose oxidase/MPO system where low continuous fluxes of H 2 O 2 are generated. HOCl-induced modifications enhance MPO binding to ECM proteins as detected by ELISA and MPO activity measurements. These data demonstrate that MPO-generated HOCl induces ECM modification by interacting with ECM proteins in a site-specific manner, and generates alterations that increase MPO adhesion. This is proposed to give rise to an increasing cycle of alterations that contribute to tissue damage.

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0 (Extracellular Matrix Proteins)
0 (Fibronectins)
126968-45-4 (Versicans)
712K4CDC10 (Hypochlorous Acid)
9007-34-5 (Collagen)
EC 1.11.1.7 (Peroxidase)

Date Created: 20200122 Date Completed: 20201130 Latest Revision: 20210119

20231215

PMC6971288

10.1038/s41598-019-57299-6

31959784