Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading

Fernández-Ruíz, Irene; Puchalska, Patrycja; Narasimhulu, Chandrakala Aluganti; Sengupta, Bhaswati; Parthasarathy, S.

doi:10.1194/jlr.m062752

Cited by 40 publications

(34 citation statements)

References 51 publications

(63 reference statements)

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“…In agreement with previous studies in murine Raw 264.7 cells [ 10 ], and in THP-1 derived macrophages [ 11 ] we demonstrated that cholesterol-containing lipid particles induce increased lipid content in macrophages derived from human THP-1 cells. On visual inspection (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…Here, we have extended previous work by others [ 10 , 11 ], by examining the susceptibility of monocyte (human THP-1) derived macrophages to uptake large quantities of lipid and cholesterol particles and vesicles (such as accumulate in more advanced fatty streaks [ 12 – 14 ]), and the subsequent effect on cell survival, cell area, cell eccentricity and relative lipid content of cells. The basic lipid particles used comprised cholesterol and lysophosphatidylcholine (LPC, a compound that is both a constituent of oxLDL [ 15 ] and that has raised levels in plasma of patients with CVD [ 16 ]).…”

Section: Introductionmentioning

confidence: 77%

“…In order to determine the molecular specificity of the effect of cholesterol on macrophages, we used four different lipid additives: cholesterol with LPC, as described with murine macrophages previously [ 10 , 11 ]; LPC alone; ergosterol with LPC; and CHS with LPC (see Fig. 6 ).…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 77%

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

et al. 2017

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“…Real-time PCR results showed that SiNPs exposure caused the up-regulated mRNA expressions of CD36 and SRA1, while down-regulated mRNA expressions in ABCA1, ABCG1, and SRB1. In addition, SiNPs had no in uence on the mRNA level of ACAT1, a critical regulator to re-esterify excessive free cholesterol to cholesterol ester to store in lipid droplets [31]. Further, 4-PBA was applied to validate the role of ER stress in the regulation of lipid homeostasis.…”

Section: Er Stress-mediated Cd36 Upregulation Involved In Lipid Accummentioning

confidence: 99%

Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE-/- mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage

Zhao

et al. 2020

Preprint

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Abstract Background: The biosafety concern of silica nanoparticles (SiNPs) is rapidly expanding alongside with its mass production and extensive applications. The cardiovascular effects of SiNPs exposure have been confirmed. However, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms. Results: We firstly investigated the in vivo effects of SiNPs exposure on atherosclerosis via intratracheal instillation of ApoE -/- mice fed a Western diet. Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) compared to the control group. Histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE -/- mice. When compared to the control, serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress was occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and CHOP expressions. Further in vitro , SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment greatly alleviated SiNPs-induced macrophage lipid accumulation, and reversed the elevated CD36 expression by SiNPs. Conclusions: Our results firstly revealed the acceleratory effect of SiNPs on the progression of atherosclerosis in ApoE -/- mice, which was related to lipid accumulation caused by ER stress-mediated upregulation of CD36 expression in macrophage.

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“…Indeed, the excess cholesterol in tissues is mainly removed through High Density Lipoproteins, which are loaded with cholesterol. Alternatively, cholesterol is removed from tissues by macrophages engulfed with dead cell membranes [26].…”

Section: Mevalonate Pathway In Different Districts Of the Bodymentioning

confidence: 99%

Mevalonate kinase deficiency: therapeutic targets, treatments, and outcomes

Marcuzzi

Piscianz

Brumatti

et al. 2017

Expert Opinion on Orphan Drugs

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Introduction: Mevalonate Kinase Deficiency (MKD) is a rare inborn disease caused by the mutation of mevalonate kinase gene. The clinical phenotype encompasses recurrent fever episodes in combination with gastrointestinal,\ud immunological, rheumatological and neurological complaints. No specific treatment is available, apart from the newly approved biologics (canakinumab), but MKD can be still considered an orphan-drug disease, since the identification of a reliable therapeutic target needs an improved knowledge on the pathogenesis of the disease, which is so far controversial.\ud Areas covered: On one hand, shortage of isoprenoid compounds downstream of mevalonate led to a defective geranylgeranylation of RhoA/Rac proteins and increased caspase-1-dependent inflammation. On the other hand, recent studies pointed the attention to the pathogenic role of the mitochondrial dysfunction and to defective production of 25-hydroxycholesterol. These mechanisms are not exclusive of each other, as they can contribute to different pathogenic features of MKD.\ud Expert opinion: Innovative therapeutic approaches to MKD may count upon various medicaments, such as isoprenoid compounds that can enter the metabolic pathway, specific enzyme inhibitors and mitochondria-\ud targeted drugs. Some of these compounds have already passed the clinical phase for other uses and may be repositioned to the treatment of MKD, fostering the development of clinical trials

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Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading

Cited by 40 publications

References 51 publications

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

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

Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE-/- mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage

Mevalonate kinase deficiency: therapeutic targets, treatments, and outcomes

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