scholarly journals Expression of the circular RNAs in astaxanthin promotes cholesterol efflux from THP-1 cells based on RNA-seq

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jie Liu ◽  
Yue Wei ◽  
Yong Lin ◽  
Peiwen Zhang ◽  
Zhexiao Zhang ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Foam Cell Formation ◽  
Sirna Transfection ◽  
Real Time Quantitative Pcr ◽  
Qrt Pcr ◽  
Oil Red O Staining

Abstract Background It is reported that circular RNAs (circRNAs) play a key role in atherosclerosis (AS). Foam cell formation, which is the main feature of AS, can be significantly inhibited by cholesterol efflux. Methods We established a model of astaxanthin (AST) promoting cholesterol efflux from macrophages through oil red O staining, real-time quantitative PCR (qRT-PCR), and western blot and used RNA sequencing to detect the expression of circRNAs in AST-treated and untreated THP-1 cells. Finally, siRNA transfection screened out circRNAs that were significantly differentially expressed. The data analysis was performed by Student’s t test and P < 0.05 was considered statistically significant. Results In the model of AST promoting cholesterol efflux from THP-1 cells, there were a total of 7276 circRNAs differentially expressed, among which the top 25 upregulated and the top 25 downregulated circRNAs were selected based on the log2 (fold change). GO analysis showed that differential expression of circRNAs in biological process (2066/3098; 66.69%), molecular function (543/3098; 17.53%), and cellular component (489/3098; 15.78%). Based on KEGG analysis, RNA transport was the most enriched pathway. Finally, we obtained 3 significantly upregulated circRNAs by siRNA transfection and qRT-PCR. Conclusions The 3 differentially expressed circRNAs may play an important role in the process of AST promoting cholesterol efflux and may be used as biomarkers to prevent AS.

scholarly journals circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Fei Xu ◽  
Li Shen ◽  
Han Chen ◽  
Rui Wang ◽  
Tongtong Zang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Circular Rnas ◽  
Foam Cell Formation ◽  
Antiatherosclerotic Effect ◽  
Progression Of Atherosclerosis

Inflammation is a crucial mediator of atherosclerosis, and several therapeutic methods that focus on inflammatory cytokines, including interleukin-1β (IL-1β), have proven effective in preventing atherogenesis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs (ncRNAs) that can exert critical functions in the regulation of atherosclerosis. Here, using circRNA sequencing, we revealed that circRNA circDENND1B (mmu_circ_0000081) is a promising novel mediator of atherosclerosis in mouse. The expression of circDENND1B is negatively related to the progression of atherosclerosis and foam cell formation, and the upregulation of circDENND1B significantly alleviates foam cell formation induced by ox-LDL by promoting cholesterol efflux. Moreover, circDENND1B participates in the anti-atherosclerotic effect of IL-1β monoclonal antibody (IL-1β mAb), both in vivo and in vitro. With bioinformatic prediction and RNA pull-down assays, we determined that circDENND1B sponges mmu-miR-17-5p to promote Abca1 expression in cells treated with IL-1β mAb. Our study revealed that circDENND1B, a novel regulator of cholesterol efflux, is a potential therapeutic target in atherosclerosis and provides new insights into the interaction between inflammation and cholesterol transport.

Abstract 43: Cholesterol Efflux Pathways Suppress Inflammasome Activation in Mice and Humans

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Marit Westerterp ◽  
Panagiotis Fotakis ◽  
Mireille Ouimet ◽  
Andrea E Bochem ◽  
Hanrui Zhang ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Inflammasome Activation ◽  
Loss Of Function ◽  
Caspase 1 ◽  
Macrophage Cholesterol Efflux

Plasma high-density-lipoprotein (HDL) has several anti-atherogenic properties, including its key role in functioning as acceptor for ATP-binding cassette A1 and G1 (ABCA1 and ABCG1) mediated cholesterol efflux. We have shown previously that macrophage Abca1/g1 deficiency accelerates atherosclerosis, by enhancing foam cell formation and inflammatory cytokine expression in atherosclerotic plaques. Macrophage cholesterol accumulation activates the inflammasome, leading to caspase-1 cleavage, required for IL-1β and IL-18 secretion. Several studies have suggested that inflammasome activation accelerates atherogenesis. We hypothesized that macrophage Abca1/g1 deficiency activates the inflammasome. In Ldlr -/- mice fed a Western type diet (WTD), macrophage Abca1/g1 deficiency increased IL-1β and IL-18 plasma levels (2-fold; P <0.001), and induced caspase-1 cleavage. Deficiency of the inflammasome components Nlrp3 or caspase-1 in macrophage Abca1/g1 knockouts reversed the increase in plasma IL-18 levels ( P <0.001), indicating these changes were inflammasome dependent. We found that macrophage Abca1/g1 deficiency induced caspase-1 cleavage in splenic CD115 + monocytes and CD11b + macrophages. While mitochondrial ROS production or lysosomal function were not affected, macrophage Abca1/g1 deficiency led to an increased splenic population of monocytes (2.5-fold; P <0.01). Monocytes secrete ATP, and as a result, ATP secretion from total splenic cells was increased (2.5-fold; P <0.01), likely contributing to inflammasome activation. Caspase-1 deficiency decreased atherosclerosis in macrophage Abca1/g1 deficient Ldlr -/- mice fed WTD for 8 weeks (225822 vs 138606 μm 2 ; P <0.05). Of therapeutic interest, one injection of reconstituted HDL (100 mg/kg) in macrophage Abca1/g1 knockouts decreased plasma IL-18 levels ( P <0.05). Tangier disease patients, with a homozygous loss-of-function for ABCA1, showed increased IL-1β and IL-18 plasma levels (3-fold; P <0.001), suggesting that cholesterol efflux pathways also suppress inflammasome activation in humans. These findings suggest that macrophage cholesterol efflux pathways suppress inflammasome activation, possibly contributing to the anti-atherogenic effects of HDL treatment.

Pomegranate peel polyphenols inhibit lipid accumulation and enhance cholesterol efflux in raw264.7 macrophages

2016 ◽  
Vol 7 (7) ◽  
pp. 3201-3210 ◽  
Author(s):  
Shengjuan Zhao ◽  
Jianke Li ◽  
Lifang Wang ◽  
Xiaoxia Wu
Keyword(s):  
Lipid Accumulation ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Pomegranate Peel ◽  
Raw264.7 Macrophages

Pomegranate peel polyphenols hindered ox-LDL-induced raw264.7 foam cell formation, by decreasing CD36 and promoting ABCA1 and LXRα expression.

scholarly journals Monocytes from HIV-infected individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration

AIDS ◽  
2015 ◽  
Vol 29 (12) ◽  
pp. 1445-1457 ◽  
Author(s):  
Anna Maisa ◽  
Anna C. Hearps ◽  
Thomas A. Angelovich ◽  
Candida F. Pereira ◽  
Jingling Zhou ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Transendothelial Migration ◽  
Foam Cell Formation

Abstract 5523: High Glucose Promotes Intracellular Lipid Accumulation by Impairing the Balance between CD36 and ATP-Binding Cassette Transporter G1 in Vascular Smooth Muscle Cells

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jia H Xue ◽  
Zu Y Yuan ◽  
Yue Wu ◽  
Yan Zhao ◽  
Wei P Zhang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Intracellular Lipid ◽  
Protein Expressions

Objective: Foam cell formation is a characteristic of atherosclerotic lesions. It’s known that high glucose promotes macrophage-derived foam cell formation involved in increased influx or reduced efflux of lipids. The aim of this study is to investigate the influence of hyperglycemia on foam cell transformation of vascular smooth muscle cells (VSMCs) and possible mechanisms contributing to these effects. Methods and Results: The results showed that high glucose in cultured human aortic SMCs increased the mRNA and protein expressions of CD36, a regulator of lipid influx, and suppressed the mRNA and protein expressions of ATP binding cassette (ABC) transporters ABCG1, a regulator of cholesterol efflux to HDL, in a dose- and time-dependent manner. However, the ability of cholesterol efflux to lipid-free apoAI was not impaired. VSMCs exposed to high glucose were easily developed into lipid-loaded cells as demonstrated by oil red O staining. Meanwhile, it had a maximum 2.3-fold increase in accumulation of esterified cholesterol compared to VSMCs cultured in normal glucose. Additionally, there was no change found in either liver X receptor (LXR)α or LXRβ, suggesting that high glucose-induced down-regulation of ABCG1 was LXR-independent. Down-regulation of ABCG1 induced by high glucose was almost totally reversed by the NF-κB inhibitors BAY 11–7085, tosyl-phenylalanine chloromethyl-ketone (TPCK) and by the antioxidant N-acetyl-L-cysteine(NAC). This reversal was accompanied by reduced intracellular lipid content. Furthermore, we also demonstrated that high glucose enhanced the binding of nuclear proteins extracted from human VSMCs to the NF-κB regulatory elements. This effect was abrogated by NAC and NF-κB inhibitors. Conclusions: These results suggested that hyperglycemia-induced foam cell formation in VSMCs was related to the imbalanced lipid flux by increasing CD36 mediated modified LDL uptake and reducing ABCG1 regulated intracellular cholesterol efflux. Moreover, this effect was associated with activated NF-κB pathway signaling.

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