Minimally oxidized LDL inhibits macrophage selective cholesteryl ester uptake and native LDL-induced foam cell formation

Meyer, Jason M.; Ji, Ailing; Cai, Lei; Westhuyzen, Deneys R. van der

doi:10.1194/jlr.m044644

Cited by 10 publications

(5 citation statements)

References 36 publications

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“…Since the discovery of the role of oxidized LDL in pathologies like atherosclerosis, some effort has been put into understanding the biological effects this lipoprotein can have, especially in pathology. Many reviews have been published on the subject, from its role in atherosclerosis [13], [91], [92], [93], apoptosis [94] and inflammation [95], its growth and proliferation promoting effects [96], its involvement on endothelial dysfunction and ageing [97], among others. Although for oxidized HDL not as much research has been done, some of its effects have also been uncovered, and it is clear that the beneficial effects of this lipoprotein can be lost following covalent modification.…”

Section: Biological Effects Of Lipoxidized Lipoproteinsmentioning

confidence: 99%

Lipoproteins as targets and markers of lipoxidation

Afonso

Spickett

2019

Redox Biology

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Lipoproteins are essential systemic lipid transport particles, composed of apolipoproteins embedded in a phospholipid and cholesterol monolayer surrounding a cargo of diverse lipid species. Many of the lipids present are susceptible to oxidative damage by lipid peroxidation, giving rise to the formation of reactive lipid peroxidation products (rLPPs). In view of the close proximity of the protein and lipid moieties within lipoproteins, the probability of adduct formation between rLPPs and amino acid residues of the proteins, a process called lipoxidation, is high. There has been interest for many years in the biological effects of such modifications, but the field has been limited to some extent by the availability of methods to determine the sites and exact nature of such modification. More recently, the availability of a wide range of antibodies to lipoxidation products, as well as advances in analytical techniques such as liquid chromatography tandem mass spectrometry (LC-MSMS), have increased our knowledge substantially. While most work has focused on LDL, oxidation of which has long been associated with pro-inflammatory responses and atherosclerosis, some studies on HDL, VLDL and Lipoprotein(a) have also been reported. As the broader topic of LDL oxidation has been reviewed previously, this review focuses on lipoxidative modifications of lipoproteins, from the historical background through to recent advances in the field. We consider the main methods of analysis for detecting rLPP adducts on apolipoproteins, including their advantages and disadvantages, as well as the biological effects of lipoxidized lipoproteins and their potential roles in diseases.

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Section: Biological Effects Of Lipoxidized Lipoproteinsmentioning

confidence: 99%

Lipoproteins as targets and markers of lipoxidation

Afonso

Spickett

2019

Redox Biology

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“…It is also associated with lipodystrophy ( 29 ). Cholesta-4,6-dien-3-one, one type of oxidized cholesterol ester, and biliverdin dihydrochloride which can reflect the metabolism of cholesterol and bile acid in the body, are associated with a range of diseases ( 30 , 31 ). In addition, previous study showed that through activating the p38MAPK and p44/42 signaling pathways, probiotic supplement inhibited PPARγ, and alleviated the obesity development and its associated metabolic disorders ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Probiotics for the Treatment of Docetaxel-Related Weight Gain of Breast Cancer Patients—A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Trial

Zhang

Yongping³

et al. 2021

Front. Nutr.

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Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients.Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy.Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]−0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = −0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = −0.917, P < 0.001) and Anaerostipes (B = −0.894, P < 0.001) were inverse correlated with the change of LDL.Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis.Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.

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“…This result is consistent with the generally accepted understanding that native (unmodified, not oxidized or acylated) LDL does not promote macrophage foam cell formation [ 44 , 45 ], particularly at the relatively low concentrations (20 μg/mL) used in the present study [ 46 ]. The use of automated image analysis to further study the effects of LDL modification on foam cell formation could provide interesting single cell and cell population results in the future, particularly with reference to work such as that by Meyer et al [ 49 ], who describe how the extent of LDL oxidation may affect macrophage response. Cells exposed to LPS in the absence of any additional source of exogenous lipid (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has been used in the preparation of pH sensitive liposomes, particularly for the delivery of oligonucleotides [ 51 , 52 ]. The concentrations of sterol-containing lipid particles in our experimental conditions were ~1000 umol/ml – at which concentrations native LDL has been found to be taken up via receptor-independent pinocytotic pathways [ 49 , 53 ]. Fluid-phase pinocytosis is known to be upregulated in human macrophages exposed to PMA [ 53 , 54 ], and to contribute to acLDL uptake in THP-1 derived macrophages [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Quantification of sterol-specific response in human macrophages using automated imaged-based analysis

et al. 2017

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BackgroundThe transformation of normal macrophage cells into lipid-laden foam cells is an important step in the progression of atherosclerosis. One major contributor to foam cell formation in vivo is the intracellular accumulation of cholesterol.MethodsHere, we report the effects of various combinations of low-density lipoprotein, sterols, lipids and other factors on human macrophages, using an automated image analysis program to quantitatively compare single cell properties, such as cell size and lipid content, in different conditions.ResultsWe observed that the addition of cholesterol caused an increase in average cell lipid content across a range of conditions. All of the sterol-lipid mixtures examined were capable of inducing increases in average cell lipid content, with variations in the distribution of the response, in cytotoxicity and in how the sterol-lipid combination interacted with other activating factors. For example, cholesterol and lipopolysaccharide acted synergistically to increase cell lipid content while also increasing cell survival compared with the addition of lipopolysaccharide alone. Additionally, ergosterol and cholesteryl hemisuccinate caused similar increases in lipid content but also exhibited considerably greater cytotoxicity than cholesterol.ConclusionsThe use of automated image analysis enables us to assess not only changes in average cell size and content, but also to rapidly and automatically compare population distributions based on simple fluorescence images. Our observations add to increasing understanding of the complex and multifactorial nature of foam-cell formation and provide a novel approach to assessing the heterogeneity of macrophage response to a variety of factors.Electronic supplementary materialThe online version of this article (10.1186/s12944-017-0629-9) contains supplementary material, which is available to authorized users.

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Minimally oxidized LDL inhibits macrophage selective cholesteryl ester uptake and native LDL-induced foam cell formation

Cited by 10 publications

References 36 publications

Lipoproteins as targets and markers of lipoxidation

Lipoproteins as targets and markers of lipoxidation

Probiotics for the Treatment of Docetaxel-Related Weight Gain of Breast Cancer Patients—A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Trial

Quantification of sterol-specific response in human macrophages using automated imaged-based analysis

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