Chrysin inhibits foam cell formation through promoting cholesterol efflux from RAW264.7 macrophages

2015 ◽  
Vol 53 (10) ◽  
pp. 1481-1487 ◽  
Author(s):  
Shuai Wang ◽  
Xue Zhang ◽  
Mingyue Liu ◽  
Hong Luan ◽  
Yubin Ji ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Raw264.7 Macrophages

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 Spiromastixones Inhibit Foam Cell Formation via Regulation of Cholesterol Efflux and Uptake in RAW264.7 Macrophages

Marine Drugs ◽  
2015 ◽  
Vol 13 (10) ◽  
pp. 6352-6365 ◽  
Author(s):  
Chongming Wu ◽  
Ran Chen ◽  
Mingyue Liu ◽  
Dong Liu ◽  
Xin Li ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Raw264.7 Macrophages

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.

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 442: D-4F, an Apolipoprotein A-I Mimetic Peptide, Protects Macrophages From Oxidized Low-Density Lipoprotein--Induced Apoptosis by Inhibiting the Endoplasmic Reticulum Stress-C/EBP Homologous Protein Pathway

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Shutong Yao ◽  
Hua Tian ◽  
Cheng Miao ◽  
Li Zhao ◽  
Peng Jiao ◽  
...  
Keyword(s):  
Er Stress ◽  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Homologous Protein ◽  
Raw264.7 Macrophages ◽  
Induced Apoptosis

Objective: D-4F, an apolipoprotein A-I (apoA-I) mimetic peptide, exerts a variety of atheroprotective functions similar to apoA-I, the major protein component of high density lipoprotein (HDL), including acting as an antioxidant, mediating cholesterol efflux from foam cells and direct anti-inflammatory effects. Our previous studies have demonstrated that endoplasmic reticulum (ER) stress promotes macrophage-derived foam cell formation by upregulating CD36 expression and mediates oxidized low-density lipoprotein (ox-LDL)-induced macrophage apoptosis. The goal of this study was to investigate the protective effect of D-4F on ox-LDL-induced macrophage cytotoxicity and specifically the ER stress-C/EBP homologous protein (CHOP) pathway-mediated apoptosis. Methods and Results: Treatment with D-4F (12.5, 25 and 50 mg/L) attenuated ox-LDL (100 mg/L)-induced cholesterol accumulation in RAW264.7 macrophages and foam cell formation in a dose-dependent manner. Similar to tunicamycin (TM), a classical ER stress inducer, ox-LDL reduced cell viability and induced apoptosis in RAW264.7 macrophages. The cytotoxic effects of ox-LDL (100 mg/L) and TM (5 mg/L) were remarkably inhibited by D-4F treatment. Interestingly, we found that D-4F also significantly suppressed the ox-LDL- and TM-induced CD36 upregulation and activation of ER stress signaling events, including the phosphorylation of inositol-requiring enzyme 1 (IRE1) and nuclear translocation of activating transcription factor 6 (ATF6). In addition, exposure of RAW264.7 macrophages to ox-LDL or TM resulted in a significant increase in the expression of CHOP, a proapoptotic transcription factor regulated by IRE1 and ATF6 under conditions of ER stress. D-4F blocked these effects in a dose-dependent manner. Moreover, administration of apoE –/– mice with D-4F (1 mg/kg per day) suppressed apoptosis and the upregulation of CD36, phospho-IRE1, GRP78 and CHOP in macrophage-dense atherosclerotic lesions. Conclusion: These data indicate that D-4F can protect macrophages from ox-LDL-induced apoptosis and that the mechanism at least partially involves its ability to inhibit the ER stress-CHOP signaling pathway.

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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