scholarly journals Resistin promotes macrophage foam cell formation in rats via dysregulation of scavenger receptors and ATP‐binding cassette transporters

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Jin‐Yi Tsai ◽  
Chun‐Yueh Lin ◽  
Yu Ru Kou ◽  
Yuh‐Lin Wu ◽  
Low‐Tone Ho ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Scavenger Receptors ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
Macrophage Foam Cell ◽  
Atp Binding Cassette Transporters ◽  
Atp Binding Cassette

Abstract 276: Shockwave Reduces Macrophage Foam Cell Formation Via Increased Expression of ATP Binding Cassette Transporters.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Wonkyoung Cho ◽  
Young Eun Yoon ◽  
Kihwan Kwon ◽  
Young Mi Park
Keyword(s):  
Western Blot ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
Mrna Levels ◽  
Macrophage Foam Cell ◽  
Migration Assay ◽  
Intracellular Cholesterol ◽  
Atp Binding Cassette

Background: Excessive lipid accumulation by macrophages plays a crucial role in atherosclerosis. Foam cells are generated by uncontrolled uptake of modified LDL, especially oxidized LDL (oxLDL), and/or impaired cholesterol efflux mediated by ATP-binding cassette (ABC) family transporters, ABCA-1 and ABCG-1. Shockwave, elicited by transient pressure disturbance, have been used for extracorporeal lithotripsy or for treating musculoskeletal disorders. Our current study suggests an evidence that shockwave may have anti-atherogenic effect by inhibiting foam cell formation. Methods/Results: Murine peritoneal macrophages were exposed to shockwaves at 0.04 mJ/mm 2 with 1000 impulses, lysed after 6, 18 and 24 hours, and tested for expression of ABCA-1 and ABCG-1. The western blot showed that shockwave induced 2.0-2.8 fold increase of ABCA-1 and ABCG-1 within 18-24 hours. mRNA levels of ABCA-1 and ABCG-1 were also increased by shockwave with 2.0 fold of peak increase in 18 hours. The increased expression of ABCA-1 and ABCG-1 was mediated by phosphorylation of ERK 1/2 (Tyr204). Western blot analysis revealed that shockwave induced phosphorylation of ERK 1/2 (Tyr204) in murine macrophages. Shockwave-induced increase of ABCA-1 and ABCG-1 was blocked by U0126 (40µM), a specific inhibitor for ERK. Oil-red O staining showed that macrophages exposed to shockwave had 25% less intracellular lipid droplets. Intracellular cholesterol measured by cholesterol oxidase and esterase revealed that macrophages exposed to shockwave had 23% less intracellular cholesterol when incubated with oxLDL (50µg/ml) for 16 hours. In vitro migration assays including modified Boyden chamber migration assay and scratch wound healing migration assay showed that macrophages exposed to shockwave had 1.2 fold more migration and had diminished migration-inhibitory effect of oxLDL. Conclusions: Shockwave reduces macrophage foam cell formation via ERK-mediated increase of ABCA-1 and ABCG-1 mediating lipid efflux and promotes macrophage migration which may induce macrophage egress from atherosclerotic lesion. Our study suggests anti-atherogenic effects of shockwave as a potential treatment modality for atherosclerosis.

scholarly journals Perivascular Adipose-Derived Exosomes Reduce Foam Cell Formation by Regulating Expression of Cholesterol Transporters

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan Liu ◽  
Yan Sun ◽  
Xuze Lin ◽  
Dai Zhang ◽  
Chengping Hu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Accumulation ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
Macrophage Foam Cell ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

Background: Accumulating evidence demonstrates that perivascular adipose tissue (PVAT) plays an important role in maintaining vascular homeostasis. The formation of macrophage foam cells is a central feature of atherosclerosis. This study aimed to evaluate the effect of PVAT-derived exosomes (EXOs) on the lipid accumulation of macrophages and verify the anti-atherogenic characteristics of PVAT.Methods and Results: We extracted EXOs from the PVAT and subcutaneous adipose tissue (SCAT) of wild-type C57BL/6J mice. After coincubation, the EXOs were taken up by RAW264.7 cells. Oil Red O staining revealed that macrophage foam cell formation and intracellular lipid accumulation were ameliorated by PVAT-EXOs. Flow cytometry showed that PVAT-EXOs significantly reduced macrophage uptake of fluorescence-labelled oxidised low-density lipoprotein (ox-LDL). In addition, high-density lipoprotein-induced cholesterol efflux was promoted by PVAT-EXOs. Western blot analysis showed the downregulation of macrophage scavenger receptor A and the upregulation of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which could be mediated by the overexpression of peroxisome proliferator-activated receptor γ and was independent of liver X receptor α.Conclusion: Our findings suggest that PVAT-EXOs reduce macrophage foam cell formation by regulating the expression of cholesterol transport proteins, which provides a novel mechanism by which PVAT protects the vasculature from atherosclerosis.

scholarly journals Lipopolysaccharide Down Regulates Both Scavenger Receptor B1 and ATP Binding Cassette Transporter A1 in RAW Cells

2002 ◽  
Vol 70 (6) ◽  
pp. 2995-3003 ◽  
Author(s):  
Irina Baranova ◽  
Tatyana Vishnyakova ◽  
Alexander Bocharov ◽  
Zhigang Chen ◽  
Alan T. Remaley ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Foam Cell ◽  
Scavenger Receptor ◽  
Control Level ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
Dependent Manner ◽  
Macrophage Foam Cell ◽  
Atp Binding Cassette

ABSTRACT Lipopolysaccharide (LPS) has recently been shown to facilitate macrophage foam cell formation and has been suggested to be a proatherogenic factor. The mechanism of LPS induced cholesterol accumulation, however, is unclear. In this report, using the macrophage-like RAW 264.7 cell line, we provide experimental evidence that LPS's proatherogenic effects may at least in part reflect altered cholesterol metabolism. Data presented demonstrate that in a dose-dependent manner, LPS is able to down regulate the mRNA expression of the two primary high-density lipoprotein (HDL) receptors, scavenger receptor B1 (SR-B1) and ATP binding cassette A1 (ABCA1), with a 50% inhibitory concentration of less than 0.2 ng/ml, as well as to decrease SR-B1 protein expression by 80%. We also found that LPS treatment resulted in a significant decrease (to 20% of the control level) of the specific 125I-HDL binding as well as in 50% inhibition of the HDL-mediated cholesterol efflux compared to untreated cells. In addition, we compared the potencies of various modified LPS preparations and demonstrated that the phosphorylated lipid A portion of LPS, which is highly conserved among gram-negative microorganisms, including Chlamydia, is primarily responsible for the effects of LPS on SR-B1 and ABCA1 expression. Inhibitors of NF-κB activation were observed to efficiently block the suppressive effect of LPS on SR-B1 and ABCA1, suggesting a mechanism involving NF-κB. These data indicate that the LPS effects on cholesterol metabolism may contribute to the proatherogenic properties of LPS.

scholarly journals Human ATP–Binding Cassette G1 Controls Macrophage Lipoprotein Lipase Bioavailability and Promotes Foam Cell Formation

2012 ◽  
Vol 32 (9) ◽  
pp. 2223-2231 ◽  
Author(s):  
Maryline Olivier ◽  
Michael W. Tanck ◽  
Ruud Out ◽  
Elise F. Villard ◽  
Bart Lammers ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
Atp Binding Cassette

scholarly journals Ablation of Galectin-12 Inhibits Atherosclerosis through Enhancement of M2 Macrophage Polarization

2020 ◽  
Vol 21 (15) ◽  
pp. 5511
Author(s):  
En-Shyh Lin ◽  
Yu-An Hsu ◽  
Ching-Yao Chang ◽  
Hui-Ju Lin ◽  
Chih Sheng Chen ◽  
...  
Keyword(s):  
Foam Cell ◽  
Macrophage Polarization ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
M2 Macrophage ◽  
Murine Macrophages ◽  
M2 Macrophage Polarization ◽  
Atp Binding Cassette

The formation of foam cells, which are macrophages that have engulfed oxidized low-density lipoprotein (OxLDL), constitutes the first stage in the development of atherosclerosis. Previously, we found that knocking down galectin-12, a negative regulator of lipolysis, leads to reduced secretion of monocyte chemoattractant protein-1 (MCP-1), a chemokine that plays an important role in atherosclerosis. This prompted us to study the role of galectin-12 in atherosclerosis. With that aim, we examined foam cell formation in Gal12‒/‒ murine macrophages exposed to OxLDL and acetylated LDL (AcLDL). Then, we generated an LDL receptor and galectin-12 double knockout (DKO) mice and studied the effect of galectin-12 on macrophage function and atherosclerosis. Lastly, we evaluated the role of galectin-12 in human THP-1 macrophages using a doxycycline-inducible conditional knockdown system. Galectin-12 knockout significantly inhibited foam cell formation in murine macrophages through the downregulation of cluster of differentiation 36 (CD36), and the upregulation of ATP Binding Cassette Subfamily A Member 1 (ABCA1), ATP Binding Cassette Subfamily G Member 1 (ABCG1), and scavenger receptor class B type 1 (SRB1). Consistent with this, galectin-12 knockdown inhibited foam cell formation in human macrophages. In addition, the ablation of galectin-12 promoted M2 macrophage polarization in human and murine macrophages as evidenced by the upregulation of the M2 marker genes, CD206 and CD163, and downregulation of the M1 cytokines, tumor necrosis factor α (TNF- α), interleukin-6 (IL-6), and MCP-1. Moreover, the ablation of galectin-12 decreased atherosclerosis formation in DKO mice. Based on these results, we propose galectin-12 as a potential therapeutic target for atherosclerosis.

ABCG subfamily of human ATP-binding cassette proteins

2002 ◽  
Vol 74 (11) ◽  
pp. 2057-2081 ◽  
Author(s):  
Stefan Lorkowski ◽  
Paul Cullen
Keyword(s):  
Abc Transporters ◽  
Foam Cell ◽  
Current Knowledge ◽  
Cell Formation ◽  
Evolutionary Relationship ◽  
The Body ◽  
High Density Lipoproteins ◽  
Foam Cell Formation ◽  
Atp Binding ◽  
Atp Binding Cassette

ATP-binding cassette (ABC) proteins form one of the largest known protein families and have been found in all known organisms. Most members of the human ABC protein family are membrane-spanning transporters that use energy derived from the hydrolysis of ATP to transport specific substrates across cell membranes. Mutations in certain human ABC transporters of the subfamilies A, B, C, and D have been shown to cause a wide variety of inherited diseases such as the lung condition cystic fibrosis, the nervous degenerative condition adrenoleukodystrophy (of Lorenzo’s Oil fame), hereditary macular degeneration of the eye (Stargardt’s disease), and inherited deficiency of circulating high-density lipoproteins (Tangier disease or familial hypoalphalipoproteinemia). Very recent studies showed that mutations in two members of the subfamily G of human ABC transporters (ABCG5 and ABCG8) cause a condition called sitosterolemia in which plant sterols accumulate in the body and may be responsible for influencing total body sterol homeostasis. In addition, other members of the subfamily G, namely ABCG1 and ABCG4, have also been shown to be involved in cellular lipid trafficking and are thought to play important roles during foam cell formation of human macrophages. By contrast, ABCG2 is a multidrug resistance transporter.In this review, we focus on the current knowledge and physiological background of the members of the subfamily G. We also present new insights on the evolutionary relationship of human and nonhuman ABCG proteins.

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