Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages
Open accessAbstract
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.
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Increased oxidative stress promotes the conversion of low-density lipoprotein (LDL) cholesterol to the more atherogenic oxidized LDL form (oxLDL).
“increased oxidative stress has been found to promote the conversion of harmful low-density lipoprotein (LDL) cholesterol to the more atherogenic oxidized LDL form (oxLDL) [148,149].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [149]
Oxidized low-density lipoprotein is linked with the occurrence of atherosclerosis.
“Oxidized low-density lipoprotein is linked with the occurrence of atherosclerosis (Lara-Guzman et al. 2018).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Lara-Guzman et al. 2018
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- [40]Oliveira C.L.P. Santos P.R. Monteiro A.M. Figueiredo Neto A.M. Effect of oxidation on the structure of human low- and high-density lipoproteins Biophys. J. 106 2014 2595 2605 24940777 PMC4070168
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“As is typically reported, e2e3 and e2e4 were protective for hypercholesterolaemia compared to e3e3 (with lower levels of “bad” cholesterol indicators; total cholesterol, LDL and APOB). e2e3 also had increased levels of “good” cholesterol indicators (HDL-cholesterol and APOA) and was associated with reduced risk of IHD…”
BackgroundInfluential
- Authors
- Lara-Guzmán, O. J., Gil-Izquierdo, Á., Medina, S., Osorio, E., Álvarez-Quintero, R., Zuluaga, N., Oger, C., Galano, J.-M., Durand, T., & Muñoz-Durango, K.
- Affiliations
- Vidarium - Centro de Investigación en Nutrición Salud y Bienestar (CO)
- Universidad de Antioquia (CO)
- École Nationale Supérieure de Chimie de Montpellier (FR)
- Corresponding author
- Muñoz-Durango, Katalina
- ORCID
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 15
- Pages
- 1-11
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC5723280
- OpenAlex
- W2770016955
- Cited by
- 194
- References
- 66
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 26 · 2023: 25 · 2022: 21 · 2021: 30 · 2020: 36 · 2019: 16 · 2018: 4
- FWCI
- 6.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Comunidad Autónoma de la Región de Murcia
- Departamento Administrativo de Ciencia, Tecnología e Innovación (528-2011, 617–2013)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- oxidized LDL, macrophages, atherosclerosis, oxidative stress, inflammation, oxylipins, isoprostanes, prostaglandins, foam cells, LDL uptake, CD36, SRA, LOX-1, THP-1 cells
- MeSH terms
- Serine-Arginine Splicing Factors, Cell Line, Foam Cells, Humans, Inflammation, Lipoproteins, LDL, Macrophages, Biomarkers, Reactive Oxygen Species, Oxidative Stress, CD36 Antigens, Atherosclerosis, Scavenger Receptors, Class E
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