Decabromodiphenyl ether (BDE-209) enhances foam cell formation in human macrophages via augmenting Toll-like receptor 4-dependent lipid uptake

2018 ◽  
Vol 121 ◽  
pp. 367-373 ◽  
Author(s):  
Hui Zhi ◽  
Jiang-Ping Wu ◽  
Lin-Ming Lu ◽  
Yan Li ◽  
Xiao-Yun Chen ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Lipid Uptake ◽  
Toll Like Receptor ◽  
Decabromodiphenyl Ether ◽  
Toll Like Receptor 4 ◽  
Human Macrophages ◽  
Bde 209

scholarly journals TLR4 (Toll-Like Receptor 4)-Dependent Signaling Drives Extracellular Catabolism of LDL (Low-Density Lipoprotein) Aggregates

2020 ◽  
Vol 40 (1) ◽  
pp. 86-102 ◽  
Author(s):  
Rajesh K. Singh ◽  
Abigail S. Haka ◽  
Arky Asmal ◽  
Valéria C. Barbosa-Lorenzi ◽  
Inna Grosheva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Knockout Mice ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Low Density ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

Objective: Aggregation and modification of LDLs (low-density lipoproteins) promote their retention and accumulation in the arteries. This is a critical initiating factor during atherosclerosis. Macrophage catabolism of agLDL (aggregated LDL) occurs using a specialized extracellular, hydrolytic compartment, the lysosomal synapse. Compartment formation by local actin polymerization and delivery of lysosomal contents by exocytosis promotes acidification of the compartment and degradation of agLDL. Internalization of metabolites, such as cholesterol, promotes foam cell formation, a process that drives atherogenesis. Furthermore, there is accumulating evidence for the involvement of TLR4 (Toll-like receptor 4) and its adaptor protein MyD88 (myeloid differentiation primary response 88) in atherosclerosis. Here, we investigated the role of TLR4 in catabolism of agLDL using the lysosomal synapse and foam cell formation. Approach and Results: Using bone marrow–derived macrophages from knockout mice, we find that TLR4 and MyD88 regulate compartment formation, lysosome exocytosis, acidification of the compartment, and foam cell formation. Using siRNA (small interfering RNA), pharmacological inhibition and knockout bone marrow–derived macrophages, we implicate SYK (spleen tyrosine kinase), PI3K (phosphoinositide 3-kinase), and Akt in agLDL catabolism using the lysosomal synapse. Using bone marrow transplantation of LDL receptor knockout mice with TLR4 knockout bone marrow, we show that deficiency of TLR4 protects macrophages from lipid accumulation during atherosclerosis. Finally, we demonstrate that macrophages in vivo form an extracellular compartment and exocytose lysosome contents similar to that observed in vitro for degradation of agLDL. Conclusions: We present a mechanism in which interaction of macrophages with agLDL initiates a TLR4 signaling pathway, resulting in formation of the lysosomal synapse, catabolism of agLDL, and lipid accumulation in vitro and in vivo.

Aged Garlic Extract Inhibits CD36 Expression and Foam Cell Formation in Human Macrophages

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
N Ide ◽  
N Morihara ◽  
L Paptheodorou ◽  
R Stirner ◽  
N Weiss
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Garlic Extract ◽  
Foam Cell Formation ◽  
Aged Garlic Extract ◽  
Human Macrophages ◽  
Cd36 Expression ◽  
Aged Garlic

scholarly journals Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

2021 ◽  
Vol 22 (5) ◽  
pp. 2529
Author(s):  
Amin Javadifar ◽  
Sahar Rastgoo ◽  
Maciej Banach ◽  
Tannaz Jamialahmadi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Special Focus ◽  
Lipid Uptake ◽  
Therapeutic Goals ◽  
Expression Of Genes

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.

Abstract 3758: Preventive Effects of Heregulin-Beta1 on Macrophage Foam Cell Formation and Atherosclerosis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takuya Watanabe ◽  
Yoshitaka Iso ◽  
Shinji Koba ◽  
Tetsuo Sakai ◽  
Gang Xu ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Apolipoprotein A1 ◽  
Foam Cell Formation ◽  
Type I ◽  
Macrophage Foam Cell ◽  
Human Macrophages ◽  
Coronary Syndrome ◽  
Atherosclerotic Lesions ◽  
Mild Hypertensive

Human heregulins, neuregulin-1 type I polypeptides known to activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, were recently found to be expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester (CE) accumulation, is modulated by scavenger receptor class A (SR-A), acyl-CoA:cholesterol acyltransferase-1 (ACAT1), and ATP-binding cassette transporter A1 (ABCA1). The present study clarified the functional roles of heregulins in macrophage foam cell formation and atherosclerosis. Plasma heregulin-beta1 levels were significantly decreased in 31 patients with acute coronary syndrome (ACS) and 33 patients with stable angina pectoris as compared with 34 mild hypertensive patients and 40 healthy volunteers (1.3+/−0.3, 2.0+/−0.4 versus 7.6+/−1.4, 8.2+/−1.2 ng/mL; at least P < 0.01). Immunoreactive heregulins and these receptor c-erbB3 were detectable within human coronary atherothrombosis obtained from ACS patients. In primary cultured human monocyte-macrophages, the expression of endogenous heregulins, heregulin-beta1, and c-erbB3 increased during monocytic differentiation into macrophages. In human macrophages differentiated by 7-day culture, exogenous heregulin-beta1, but not heregulin-alpha, significantly reduced acetylated low-density lipoprotein (acLDL)-induced CE accumulation by reducing SR-A and ACAT1 expression and by increasing ABCA1 expression at both mRNA and protein levels. Heregulin-beta1 significantly decreased endocytic uptake of [ 125 I]acLDL and increased cholesterol efflux by apolipoprotein A1 from human macrophages. Chronic infusion of heregulin-beta1 by osmotic mini-pumps into apolipoprotein E-deficient mice significantly suppressed the progression of macrophage-driven atherosclerotic lesions by 64%. Our study provides the first evidence that heregulin-beta1 may participate in anti-atherogenesis by suppressing macrophage foam cell formation via SR-A and ACAT1 down-regulation and ABCA1 up-regulation.

Epigallocatechin-3-gallate Reduces Scavenger Receptor A Expression and Foam Cell Formation in Human Macrophages

2017 ◽  
Vol 65 (15) ◽  
pp. 3141-3150 ◽  
Author(s):  
Sy-Jou Chen ◽  
Yung-Hsi Kao ◽  
Li Jing ◽  
Yi-Ping Chuang ◽  
Wan-Lin Wu ◽  
...  
Keyword(s):  
Foam Cell ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Human Macrophages ◽  
Scavenger Receptor A

The activation of liver X receptors inhibits toll-like receptor-9-induced foam cell formation

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Rosalinda Sorrentino ◽  
Silvana Morello ◽  
Eduardo Bonavita ◽  
Aldo Pinto
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Liver X Receptors ◽  
Toll Like Receptor ◽  
X Receptors
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