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Syed Saad Hussain, Megan T Harris, Alex J B Kreutzberger, Candice M Inouye, Catherine A Doyle, Anna M Castle, Peter Arvan, J David Castle
In pancreatic β cells, insulin granule membranes are enriched in cholesterol and are both recycled and newly generated. Cholesterol's role in supporting granule membrane formation and function is poorly understood.<u>A</u>TP<u>b</u>inding<u>c</u>assette transporters ABCG1 and ABCA1 regulate intracellular cholesterol and are important for insulin secretion. RNAi-induced depletion in cultured pancreatic β cells shows that ABCG1 is needed to stabilize newly made insulin granules against lysosomal degradation; ABCA1 is also involved but to a lesser extent...
March 14, 2018: Molecular Biology of the Cell
Caixia Guo, Ru Ma, Xiaoying Liu, Tian Chen, Yang Li, Yang Yu, Junchao Duan, Xianqing Zhou, Yanbo Li, Zhiwei Sun
Oxidized low-density lipoprotein (oxLDL), a marker of hyperlipidemia, plays a pivotal role in the development of atherosclerosis through the induction of macrophage-derived foam cell formation and thereafter apoptosis. Previous studies have indicated that silica nanoparticle (SiNPs) may exert a proatherogenic role, which could induce endothelial dysfunction, and monocytes infiltration. However, little is known about SiNPs' effects on macrophage-derived foam cell formation and apoptosis in the pathogenesis of atherosclerosis...
March 10, 2018: Science of the Total Environment
Michelle S M A Damen, Jéssica Cristina Dos Santos, Rob Hermsen, J Adam van der Vliet, Mihai G Netea, Niels P Riksen, Charles A Dinarello, Leo A B Joosten, Bas Heinhuis
BACKGROUND AND AIMS: The role of interleukin (IL-)32 in inflammatory conditions is well-established, however, the mechanism behind its role in atherosclerosis remains unexplained. Our group reported a promoter single nucleotide polymorphism in IL-32 associated with higher high-density lipoprotein (HDL) concentrations. We hypothesize that endogenous IL-32 in liver cells, a human monocytic cell line and carotid plaque tissue, can affect atherosclerosis by regulating (HDL) cholesterol homeostasis via expression of cholesterol transporters/mediators...
March 2, 2018: Atherosclerosis
Yi Zeng, Yi Peng, Kun Tang, Yu Qin Wang, Zhe Yu Zhao, Xin Yu Wei, Xiao Le Xu
As the most abundant flavonoid in Ampelopsis grossedentata, the protective effects of dihydromyricetin on atherosclerosis have been well established, yet the detailed mechanisms are not fully understood. The aim of the present study was to examine the effect of dihydromyricetin on lipid accumulation and the underlying molecular mechanisms in macrophages and ApoE-/- mice. Incubation with dihydromyricetin significantly attenuated oxidized low-density lipoprotein (ox-LDL)-mediated cholesterol and lipid accumulation in THP-1-derived macrophages, which was due to increased cholesterol efflux...
March 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zulong Xie, Xuedong Wang, Xinxin Liu, Huaan Du, Changbin Sun, Xin Shao, Jiangtian Tian, Xia Gu, Hailong Wang, Jinwei Tian, Bo Yu
BACKGROUND: Obesity is causally associated with atherosclerosis, and adipose tissue (AT)-derived exosomes may be implicated in the metabolic complications of obesity. However, the precise role of AT-exosomes in atherogenesis remains unclear. We herein aimed to assess the effect of AT-exosomes on macrophage foam cell formation and polarization and subsequent atherosclerosis development. METHODS AND RESULTS: Four types of exosomes isolated from the supernatants of ex vivo subcutaneous AT and visceral AT (VAT) explants that were derived from wild-type mice and high-fat diet (HFD)-induced obese mice were effectively taken up by RAW264...
March 3, 2018: Journal of the American Heart Association
Kelli Monteiro da Costa, Raphael C Valente, Eduardo J Salustiano, Luciana B Gentile, Leonardo Freire-de-Lima, Lucia Mendonça-Previato, José O Previato
Chagas disease is a neglected disease caused by the protozoan Trypanosoma cruzi and affects 8 million people worldwide. The main chemotherapy is based on benznidazole. The efficacy in the treatment depends on factors such as the parasite strain, which may present different sensitivity to treatment. In this context, the expression of ABC transporters has been related to chemotherapy failure. ABC transporters share a well-conserved ABC domain, responsible for ATP binding and hydrolysis, whose the energy released is coupled to transport of molecules through membranes...
2018: Frontiers in Microbiology
Ibragim Gaidarov, Todd Anthony, Joel Gatlin, Xiaohua Chen, David Mills, Michelle Solomon, Sangdon Han, Graeme Semple, David J Unett
GPR84 is an orphan G-protein coupled receptor, expressed on monocytes, macrophages and neutrophils and is significantly upregulated by inflammatory stimuli. The physiological role of GPR84 remains largely unknown. Medium chain fatty acids (MCFA) activate the receptor and have been proposed to be its endogenous ligands, although the high concentrations of MCFAs required for receptor activation generally exceed normal physiological levels. We identified the natural product embelin as a highly potent and selective surrogate GPR84 agonist (originally disclosed in patent application WO2007027661A2, 2007) and synthesized close structural analogs with widely varying receptor activities...
February 19, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Katalin Völgyi, Kata Badics, Fernando J Sialana, Péter Gulyássy, Edina Brigitta Udvari, Viktor Kis, László Drahos, Gert Lubec, Katalin Adrienna Kékesi, Gábor Juhász
Intracellular β-amyloid (Aβ) accumulation is an early event in Alzheimer's disease (AD) progression. Recently, it has been uncovered that presenilins (PSs), the key components of the amyloid precursor protein (APP) processing and the β-amyloid producing γ-secretase complex, are highly enriched in a special sub-compartment of the endoplasmic reticulum (ER) functionally connected to mitochondria, called mitochondria-associated ER membrane (MAM). A current hypothesis of pathogenesis of Alzheimer's diseases (AD) suggests that MAM is involved in the initial phase of AD...
February 22, 2018: Molecular Neurobiology
Elmar W Tobi, Roderick C Slieker, René Luijk, Koen F Dekkers, Aryeh D Stein, Kate M Xu, P Eline Slagboom, Erik W van Zwet, L H Lumey, Bastiaan T Heijmans
Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis...
January 2018: Science Advances
Chuanrui Ma, Wenwen Zhang, Xiaoxiao Yang, Ying Liu, Lipei Liu, Ke Feng, Xiaomeng Zhang, Shu Yang, Lei Sun, Miao Yu, Jie Yang, Xiaoju Li, Wenquan Hu, Robert Q Miao, Yan Zhu, Luyuan Li, Jihong Han, Yuanli Chen, Yajun Duan
BACKGROUND AND PURPOSE: LXR agonist (T317) reduces atherosclerosis while inducing fatty liver. Metformin activates energy metabolism by activating AMPKα. In this study, we determined if the interaction between metformin and T317 can inhibit atherosclerosis without activation of hepatic lipogenesis. EXPERIMENTAL APPROACH: ApoE deficient mice were treated with T317, metformin or both contained in a high-fat diet for 16 weeks. After treatment, mouse aorta, liver, macrophage and serum samples were collected to determine atherosclerotic lesions, fatty liver, lipid profiles and expression of related molecules...
February 2, 2018: British Journal of Pharmacology
Yongqiang Li, Shuxin Shen, Shoukun Ding, Lixia Wang
Atherosclerosis is a chronic inflammatory disease, which is triggered by lipid retention. Toll-like receptor 2 (TLR2) is a novel target for therapeutic intervention in atherosclerosis. In addition, nuclear factor-κB (NF-κB) serves important roles in stress response and inflammation. The present study investigated whether TLR2 is involved in the activation of cholesterol efflux in macrophages by regulating the NF-κB pathway. The human monocytic THP-1 cell line and murine macrophage RAW264.7 cell line were treated with 50 µg/ml oxidized low-density lipoprotein (ox-LDL) for 48 h in order to obtain macrophage foam cells...
January 2018: Experimental and Therapeutic Medicine
Xiao-Xiao Liu, Xiao-Wen Zhang, Kai Wang, Xue-Ying Wang, Wen-Long Ma, Wei Cao, Dan Mo, Yang Sun, Xiao-Qiang Li
BACKGROUND: Atherosclerosis is characterized by chronic inflammation in vascular wall. Previous studies suggest that Kuwanon G (KWG) exerts anti-inflammatory activities. However, the effect of KWG on atherosclerosis remains unexplored. AIMS: To explore whether KWG affects macrophage foam cell formation in vitro and atherogenesis in vivo. METHODS: RAW 264.7 macrophages were stimulated with ox-LDL for 24h to induce foam cell formation and treated with KWG...
January 17, 2018: Toxicology and Applied Pharmacology
Shereen M Aleidi, Alryel Yang, Laura J Sharpe, Geetha Rao, Blake J Cochran, Kerry-Anne Rye, Maaike Kockx, Andrew J Brown, Ingrid C Gelissen
The ABC lipid transporters, ABCA1 and ABCG1, are essential for maintaining lipid homeostasis in cells such as macrophages by exporting excess cholesterol to extracellular acceptors. These transporters are highly regulated at the post-translational level, including protein ubiquitination. Our aim was to investigate the role of the E3 ubiquitin ligase HECTD1, recently identified as associated with ABCG1, on ABCG1 and ABCA1 protein levels and cholesterol export function. Here, we show that HECTD1 protein is widely expressed in a range of human and murine primary cells and cell lines, including macrophages, neuronal cells and insulin secreting β-cells...
January 3, 2018: Biochimica et Biophysica Acta
Hung-Chih Lin, Chong-Kuei Lii, Hui-Chun Chen, Ai-Hsuan Lin, Ya-Chen Yang, Haw-Wen Chen
oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells...
January 3, 2018: American Journal of Chinese Medicine
Jah Yeon Choi, Jiheun Ryu, Hyun Jung Kim, Joon Woo Song, Joo Hee Jeon, Dae-Hee Lee, Dong Joo Oh, Dae-Gab Gweon, Wang-Yuhl Oh, Hongki Yoo, Kyeongsoon Park, Jin Won Kim
Rationale: Atherosclerotic plaque is a chronic inflammatory disorder involving lipid accumulation within arterial walls. In particular, macrophages mediate plaque progression and rupture. While PPARγ agonist is known to have favorable pleiotropic effects on atherogenesis, its clinical application has been very limited due to undesirable systemic effects. We hypothesized that the specific delivery of a PPARγ agonist to inflamed plaques could reduce plaque burden and inflammation without systemic adverse effects...
2018: Theranostics
Petteri Rinne, James J Kadiri, Mauricio Velasco-Delgado, Salla Nuutinen, Miro Viitala, Maija Hollmén, Martina Rami, Eriika Savontaus, Sabine Steffens
OBJECTIVE: The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis...
December 28, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Willem J M Mulder, Mandy M T van Leent, Marnix Lameijer, Edward A Fisher, Zahi A Fayad, Carlos Pérez-Medina
Nature is an inspirational source for biomedical engineering developments. Particularly, numerous nanotechnological approaches have been derived from biological concepts. For example, among many different biological nanosized materials, viruses have been extensively studied and utilized, while exosome research has gained much traction in the 21st century. In our body, fat is transported by lipoproteins, intriguing supramolecular nanostructures that have important roles in cell function, lipid metabolism, and disease...
December 27, 2017: Accounts of Chemical Research
Jiesi Xu, Yang Xu, Yanyong Xu, Liya Yin, Yanqiao Zhang
Atherosclerotic cardiovascular disease is a leading cause of death in the western world. Increased plasma triglyceride and cholesterol levels are major risk factors for this disease. Carboxylesterase 1 (Ces1/Ces1g) has been shown to play a role in metabolic control. So far, the role of mouse Ces1/Ces1g deficiency in atherosclerosis is not elucidated. We generated Ces1/Ces1g -/- mice. Compared to wild-type mice, Ces1/Ces1g -/- mice had reduced plasma cholesterol levels. We then generated Ces1g -/- Ldlr -/- double knockout (DKO) mice, which were fed a Western diet for 16 weeks...
December 19, 2017: Scientific Reports
Javier Sáenz, Gonzalo Alba, María E Reyes-Quiroz, Isabel Geniz, Juan Jiménez, Francisco Sobrino, Consuelo Santa-María
Liver X receptor alpha (LXRα) is a nuclear receptor involved in cholesterol homeostasis. Curcumin, a traditional Chinese derivative from the rhizomes of Curcuma longa and a well-known AMP-activated protein kinase (AMPK) activator, possess hypocholesterolemic activity, however, the possible link between AMPK and cholesterol is unknown. In this study, we have investigated whether curcumin regulates metabolic changes in cholesterol metabolism via LXRα in THP-1 human macrophages, the cells implicated in atheroma plaques formation...
November 16, 2017: Journal of Nutritional Biochemistry
Silvia Castiglioni, Matteo Monti, Giuditta Ainis Buscherini, Lorenzo Arnaboldi, Monica Canavesi, Alberto Corsini, Stefano Bellosta
The data presented in this article is related to the research article entitled " ABCA1 and HDL3 are Required to Modulate Smooth Muscle Cells Phenotypic Switch after Cholesterol Loading " (Castiglioni et al., 2017) [1]. This data describes the characterization of the phenotypic changes induced by cholesterol loading in smooth muscle cells (SMCs) isolated from the aortae of C57BL/6 mice. Upon cholesterol loading, there is a significant and concentration-dependent decrease in the expression of Acta2 and a parallel increase in Mac-2, and ATP binding cassette (ABC) transporters Abca1 and Abcg1 ...
February 2018: Data in Brief
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