Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages

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Abstract

Oxidized low-density lipoprotein (oxLDL) is a well-recognized proatherogenic particle that functions in atherosclerosis. In this study, we established conditions to generate human oxLDL, characterized according to the grade of lipid and protein oxidation, particle size and oxylipin content. The induction effect of the cellular proatherogenic response was assessed in foam cells by using an oxLDL-macrophage interaction model. Uptake of oxLDL, reactive oxygen species production and expression of oxLDL receptors (CD36, SR-A and LOX-1) were significantly increased in THP-1 macrophages. Analyses of 35 oxylipins revealed that isoprostanes (IsoP) and prostaglandins (PGs) derived from the oxidation of arachidonic, dihomo gamma-linolenic and eicosapentaenoic acids were strongly and significantly induced in macrophages stimulated with oxLDL. Importantly, the main metabolites responsible for the THP1-macrophage response to oxLDL exposure were the oxidative stress markers 5- epi-5-F _2t-IsoP, 15-E _1t-IsoP, 8-F _3t-IsoP and 15-keto-15-F _2t-IsoP as well as inflammatory markers PGDM, 17- trans-PGF _3α, and 11β-PGF _2α, all of which are reported here, for the first time, to function in the interaction of oxLDL with THP-1 macrophages. By contrast, a salvage pathway mediated by anti-inflammatory PGs (PGE ₁ and 17- trans-PGF _3α) was also identified, suggesting a response to oxLDL-induced injury. In conclusion, when THP-1 macrophages were treated with oxLDL, a specific induction of biomarkers related to oxidative stress and inflammation was triggered. This work contributes to our understanding of initial atherogenic events mediated by oxLDL-macrophage interactions and helps to generate new approaches for their modulation.

Graphical abstract

Highlights

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OxLDL has a potent impact on the oxylipin profiles in THP-1 human macrophages.
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OxLDL induces biomarkers of oxidation and inflammation in THP-1 human macrophages.
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Human Macrophages produce anti-inflammatory prostaglandins after oxLDL exposure.

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Most cited references 53

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Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages.

Vidya Kunjathoor, Maria Febbraio, Eugene A. Podrez … (2002)

Modification of low density lipoprotein (LDL) can result in the avid uptake of these lipoproteins via a family of macrophage transmembrane proteins referred to as scavenger receptors (SRs). The genetic inactivation of either of two SR family members, SR-A or CD36, has been shown previously to reduce oxidized LDL uptake in vitro and atherosclerotic lesions in mice. Several other SRs are reported to bind modified LDL, but their contribution to macrophage lipid accumulation is uncertain. We generated mice lacking both SR-A and CD36 to determine their combined impact on macrophage lipid uptake and to assess the contribution of other SRs to this process. We show that SR-A and CD36 account for 75-90% of degradation of LDL modified by acetylation or oxidation. Cholesteryl ester derived from modified lipoproteins fails to accumulate in macrophages taken from the double null mice, as assessed by histochemistry and gas chromatography-mass spectrometry. These results demonstrate that SR-A and CD36 are responsible for the preponderance of modified LDL uptake in macrophages and that other scavenger receptors do not compensate for their absence.

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Record: found
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Isoprostane generation and function.

Ginger L Milne, Huiyong Yin, Klarissa D Hardy … (2011)

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Record: found
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The LDL modification hypothesis of atherogenesis: an update.

Daniel Steinberg (2009)

The accumulated evidence that oxidative modification of LDL plays an important role in the pathogenesis of atherosclerosis in animal models is very strong. The negative results in recent clinical studies have caused many to conclude that LDL oxidation may not be relevant in the human disease. Yet many of the lines of evidence that support the hypothesis have been demonstrated to apply also in humans. In this review, we briefly summarize the lines of evidence on which the hypothesis rests, its strengths, and its weaknesses.

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Author and article information

Contributors

Katalina Muñoz-Durango

Journal

Journal ID (nlm-ta): Redox Biol

Journal ID (iso-abbrev): Redox Biol

Title: Redox Biology

Publisher: Elsevier

ISSN (Electronic): 2213-2317

Publication date PMC-release: 22 November 2017

Publication date Collection: May 2018

Publication date (Electronic): 22 November 2017

Volume: 15

Pages: 1-11

Affiliations

[a ]Vidarium, Nutrition, Health and Wellness Research Center, Nutresa Business Group. Calle 8 Sur No. 50-67, Medellín, Colombia

[b ]Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, 30100 Campus University Espinardo, Murcia, Spain

[c ]Grupo de Investigación en Sustancias Bioactivas, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia, Calle 70 No. 52-21, Medellín, Colombia

[d ]Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, University of Montpellier, ENSCM, Faculty of Pharmacy, Montpellier, France

Author notes

[* ]Corresponding author. kmunoz@ 123456serviciosnutresa.com

Article

Publisher ID: S2213-2317(17)30718-8

DOI: 10.1016/j.redox.2017.11.017

PMC ID: 5723280

PubMed ID: 29195136

SO-VID: fe38f4eb-7c00-4b8f-9bfc-c24c2a3240e8

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 27 September 2017

Date revision received : 1 November 2017

Date accepted : 18 November 2017

Categories

Subject: Research Paper

Keywords: aa, arachidonic acid,aaph, 2,2′-azobis (2-methylpropionamidine) dihydrochloride,bht, butylated hydroxytoluene,bmi, body mass index,cvd, cardiovascular diseases,c-smp, cell-surface marker proteins,dgla, dihomo-gamma-linolenic acid,dls, dynamic light scattering,etda, ethylenediaminetetraacetic acid,epa, eicosapentaenoic acid,esi, electrospray ionization,frap, ferric reducing antioxidant power assay,isop, isoprostane,ldl, low-density lipoprotein,ldh, lactate dehydrogenase,lc, liquid chromatography,oxldl, oxidized low-density lipoprotein,mda, malondialdehyde,mfi, mean fluorescence intensity,mrm, multiple reaction monitoring,ms, mass spectrometry,os, oxidative stress,pbs, phosphate-buffered saline,pma, phorbol 12-myristate-13-acetate,pgs, prostaglandins,pufa, polyunsaturated fatty acids,rem, relative electrophoretic mobility,ros, reactive oxygen species,spe, solid phase extraction,sr, scavenger receptor,tbars, thiobarbituric acid-reactive substances,tlr, toll-like receptor,trolox, (±)−6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid,tx, thromboxane,uhplc, ultra-high performance liquid chromatography,macrophages,oxldl,oxylipins,isoprostanes,prostaglandins,foam cells

Data availability:

Keywords: aa, arachidonic acid, aaph, 2,2′-azobis (2-methylpropionamidine) dihydrochloride, bht, butylated hydroxytoluene, bmi, body mass index, cvd, cardiovascular diseases, c-smp, cell-surface marker proteins, dgla, dihomo-gamma-linolenic acid, dls, dynamic light scattering, etda, ethylenediaminetetraacetic acid, epa, eicosapentaenoic acid, esi, electrospray ionization, frap, ferric reducing antioxidant power assay, isop, isoprostane, ldl, low-density lipoprotein, ldh, lactate dehydrogenase, lc, liquid chromatography, oxldl, oxidized low-density lipoprotein, mda, malondialdehyde, mfi, mean fluorescence intensity, mrm, multiple reaction monitoring, ms, mass spectrometry, os, oxidative stress, pbs, phosphate-buffered saline, pma, phorbol 12-myristate-13-acetate, pgs, prostaglandins, pufa, polyunsaturated fatty acids, rem, relative electrophoretic mobility, ros, reactive oxygen species, spe, solid phase extraction, sr, scavenger receptor, tbars, thiobarbituric acid-reactive substances, tlr, toll-like receptor, trolox, (±)−6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid, tx, thromboxane, uhplc, ultra-high performance liquid chromatography, macrophages, oxldl, oxylipins, isoprostanes, prostaglandins, foam cells