Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis

Ismael, FO; Proudfoot, JM; Brown, BE; Van Reyk, DM; Croft, KD; Davies, MJ; Hawkins, CL

Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis

Ismael, FO Proudfoot, JM Brown, BE Van Reyk, DM

Croft, KD Davies, MJ Hawkins, CL

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Publication Type:: Journal Article
Citation:: Archives of Biochemistry and Biophysics, 2015, 573 pp. 40 - 51
Issue Date:: 2015-05-01

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Field	Value	Language
dc.contributor.author	Ismael, FO	en_US
dc.contributor.author	Proudfoot, JM	en_US
dc.contributor.author	Brown, BE	en_US
dc.contributor.author	Van Reyk, DM https://orcid.org/0000-0002-7768-8662	en_US
dc.contributor.author	Croft, KD	en_US
dc.contributor.author	Davies, MJ	en_US
dc.contributor.author	Hawkins, CL	en_US
dc.date.available	2020-05-25T19:11:19Z
dc.date.issued	2015-05-01	en_US
dc.identifier.citation	Archives of Biochemistry and Biophysics, 2015, 573 pp. 40 - 51	en_US
dc.identifier.issn	0003-9861	en_US
dc.identifier.uri	http://hdl.handle.net/10453/34711
dc.description.abstract	© 2015 Elsevier Inc. All rights reserved. Abstract Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces oxidants that are implicated in atherosclerosis. Modification of LDL by the MPO oxidant hypochlorous acid (HOCl), results in extensive lipid accumulation by macrophages. However, the reactivity of the other major MPO oxidant, hypothiocyanous acid (HOSCN) with LDL is poorly characterised, which is significant given that thiocyanate is the favoured substrate for MPO. In this study, we comprehensively compare the reactivity of HOCl and HOSCN with LDL, and show key differences in the profile of oxidative damage observed. HOSCN selectively modifies Cys residues on apolipoprotein B100, and oxidises cholesteryl esters resulting in formation of lipid hydroperoxides, 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and F2-isoprostanes. The modification of LDL by HOSCN results macrophage lipid accumulation, though generally to a lesser extent than HOCl-modified LDL. This suggests that a change in the ratio of HOSCN:HOCl formation by MPO from variations in plasma thiocyanate levels, will influence the nature of LDL oxidation in vivo, and has implications for the progression of atherosclerosis.	en_US
dc.relation.ispartof	Archives of Biochemistry and Biophysics	en_US
dc.relation.isbasedon	10.1016/j.abb.2015.03.008	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Cell Line	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Foam Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Hypochlorous Acid	en_US
dc.subject.mesh	Thiocyanates	en_US
dc.subject.mesh	Cholesterol	en_US
dc.subject.mesh	Cholesterol Esters	en_US
dc.subject.mesh	Peroxidase	en_US
dc.subject.mesh	Lipoproteins, LDL	en_US
dc.subject.mesh	Oxidants	en_US
dc.subject.mesh	Oxidation-Reduction	en_US
dc.subject.mesh	Atherosclerosis	en_US
dc.subject.mesh	Apolipoprotein B-100	en_US
dc.title	Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis	en_US
dc.type	Journal Article
utslib.citation.volume	573	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	573	en_US

Abstract:

© 2015 Elsevier Inc. All rights reserved. Abstract Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces oxidants that are implicated in atherosclerosis. Modification of LDL by the MPO oxidant hypochlorous acid (HOCl), results in extensive lipid accumulation by macrophages. However, the reactivity of the other major MPO oxidant, hypothiocyanous acid (HOSCN) with LDL is poorly characterised, which is significant given that thiocyanate is the favoured substrate for MPO. In this study, we comprehensively compare the reactivity of HOCl and HOSCN with LDL, and show key differences in the profile of oxidative damage observed. HOSCN selectively modifies Cys residues on apolipoprotein B100, and oxidises cholesteryl esters resulting in formation of lipid hydroperoxides, 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and F2-isoprostanes. The modification of LDL by HOSCN results macrophage lipid accumulation, though generally to a lesser extent than HOCl-modified LDL. This suggests that a change in the ratio of HOSCN:HOCl formation by MPO from variations in plasma thiocyanate levels, will influence the nature of LDL oxidation in vivo, and has implications for the progression of atherosclerosis.

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http://hdl.handle.net/10453/34711