Macrophage/foam cell is an attribute of inflammation: Mechanisms of formation and functional role

Душкин, М. И.

doi:10.1134/s0006297912040025

Cited by 28 publications

(21 citation statements)

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“…Moreover, these lipid-laden foam cells, present from the earliest discernable fatty streak lesions to advanced complicated lesions and plaque disruption, are key regulators of the pathological behavior of plaques [1][2][3][4][5]47) . Hence, reducing the formation of foam cells may be an efficient strategy for treating and preventing atherosclerosis 4) .…”

Section: Discussionmentioning

confidence: 99%

“…Our findings are consistent with a recent report by Lu et al 34) who found that erythropoietin suppresses foam cell formation via the LXR -dependent upregulation of ABCA1 and ABCG1. In addition, numerous studies have reported the close link between lipid homeostasis and inflammation in macrophages 3) . Thus, we examined the effect of UFM1 on the inflammatory response in the formation of macrophage foam cell.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…A sample of 100 L was used to determine the 3 H radioactivity of cells and protein content. Efflux is expressed as the percentage of 3 H cholesterol in medium/( 3 H cholesterol in medium 3 H cholesterol in cells) 100%. Cellular protein concentration estimation was used to normalize the efflux.…”

Section: Cholesterol Efflux Assaysmentioning

confidence: 99%

“…The accumulation of lipid-laden macrophage foam cells is the major hallmark of early stage atherosclerotic lesions 2) . Moreover, excessive lipid accumulation in macrophages of the arterial intima drives the secretion of proinflammatory mediators, potentiating atherogenesis 3) . Lipid homeostasis, particularly cholesterol homeostasis, is a critical step in the formation of macrophage foam cells 4,5) .…”

Section: Introductionmentioning

confidence: 99%

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UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

Pang

Xiong

et al. 2015

J Atheroscler Thromb

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Aim: Macrophage foam cell formation is the most prominent characteristic of the early stages of atherosclerosis. Ubiquitin Fold Modifier 1 (UFM1) is a new member of the ubiquitin-like protein family, and its underlying mechanism of action in macrophage foam cell formation is poorly understood. Our current study focuses on UFM1 and investigates its role in macrophage foam cell formation. Methods: Using real-time quantitative PCR (qRT-PCR) and western blot analysis, we first analyzed the UFM1 expression in mouse peritoneal macrophages (MPMs) from ApoE / mice in vivo and in human macrophages treated with oxLDL in vitro. Subsequently, the effects of UFM1 on macrophages foam cell formation were determined by Nile Red staining and direct lipid analysis. We then examined whether UFM1 affects the process of lipid metabolism in macrophages. Lastly, with the method of small interfering RNA (siRNA), we delineated the mechanism of UFM1 to attenuate lipid accumulation in THP-1 macrophages. Results: UFM1 is dramatically upregulated under atherosclerosis conditions both in vivo and in vitro. Moreover, UFM1 markedly decreased macrophage foam cell formation. Mechanistic studies revealed that UFM1 increased the macrophage cholesterol efflux, which was due to the increased expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1). Furthermore, the upregulation of ABCA1 and ABCG1 by UFM1 resulted from liver X receptor (LXR ) activation, which was confirmed by the observation that LXR siRNA prevented the expression of ABCA1 and ABCG1. Consistent with this, the UFM1-mediated attenuation of lipid accumulation was abolished by such inhibition. Conclusions: Taken together, our results showed that UFM1 could suppress foam cell formation via the LXR -dependent pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Acknowledgmentsmentioning

confidence: 99%

Section: Cholesterol Efflux Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

Pang

Xiong

et al. 2015

J Atheroscler Thromb

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“…Reboldi et al found that Ch25h-25-HC suppresses NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome-dependent interleukin-1β (IL-1β) production in macrophages and inhibits septic shock in mouse models 13 . Sterol regulatory element binding protein 2 (SREBP2) and liver X receptor (LXR) are two TFs that regulate cholesterol biosynthesis and metabolism reciprocally 14 . SREBP2 is a key mediator of genes involved in cholesterol biosynthesis [e.g., 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase] and uptake [e.g., low density lipoprotein (LDL) receptor] as well as induces NLRP3 inflammasome in ECs 15 .…”

Section: Introductionmentioning

confidence: 99%

Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility

Martin

Zhang

et al. 2017

Circulation

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Background Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall [e.g., endothelial cells (ECs)] as well as circulating and resident immunogenic cells (e.g., monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of sterol regulatory element binding protein 2 (SREBP2), 25-hydroxycholesterol (25-HC) and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages. Methods Bioinformatic analyses were used to investigate RNA-seq data to identify cholesterol oxidation and efflux genes regulated by KLF4. In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR. Results Vasoprotective stimuli increased the expression of Ch25h and LXR via krüppel-like factor 4 (KLF4). The KLF4-Ch25h/LXR homeostatic axis functions through suppressing inflammation, evidenced by the reduction of inflammasome activity in ECs and the promotion of M1 to M2 phenotypic transition in macrophages. The increased atherosclerosis in ApoE−/−/Ch25h−/− mice further demonstrates the beneficial role of the KLF4-Ch25h/LXR axis in vascular function and disease. Conclusions KLF4 transactivates Ch25h and LXR thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility.

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Icariin Inhibits Foam Cell Formation by Down‐Regulating the Expression of CD36 and Up‐Regulating the Expression of SR‐BI

Huang

Yan

Peng

et al. 2015

J of Cellular Biochemistry

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Icariin is an important pharmacologically active flavonol diglycoside that can inhibit inflammation in lipopolysaccharide (LPS)-stimulated macrophages. However, little is known about the molecular mechanisms underlying the inhibitory effect of Icariin in the formation of foam cells. In this study, macrophages were cultured with LPS and oxidized low-density lipoprotein (oxLDL) in the presence or absence of Icariin. RT-PCR and western blot were used to detect the levels of mRNA and protein expression of CD36, scavenger receptor class B type I (SR-BI) and the phosphorylation of p38MAPK. It was demonstrated that 4 µM or 20 µM Icariin treatment significantly inhibited the cholesterol ester (CE)/total cholesterol (TC) and oxLDL-mediated foam cell formation (P < 0.05). The binding of oxLDL to LPS-activated macrophages was also significantly hindered by Icariin (P < 0.05). Furthermore, Icariin down-regulated the expression of CD36 in LPS-activated macrophages in a dose-dependent manner and CD36 over-expression restored the inhibitory effect of Icariin on foam cell formation. The phosphorylation of p38MAPK was reduced by Icariin, indicating that Icariin reduced the expression of CD36 through the p38MAPK pathway. In addition, Icariin up-regulated SR-BI protein expression in a dose-dependent manner, and SR-BI gene silencing restored the inhibitory effect of Icariin on foam cell formation. These data demonstrate that Icariin inhibited foam cell formation by down-regulating the expression of CD36 and up-regulating the expression of SR-BI. Therefore, our findings provide a new explanation as to why Icariin could inhibit atherosclerosis.

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Macrophage/foam cell is an attribute of inflammation: Mechanisms of formation and functional role

Cited by 28 publications

References 100 publications

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility

Icariin Inhibits Foam Cell Formation by Down‐Regulating the Expression of CD36 and Up‐Regulating the Expression of SR‐BI

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