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Chao-Qiang Lai, Mary K Wojczynski, Laurence D Parnell, Bertha A Hidalgo, Marguerite Ryan Irvin, Stella Aslibekyan, Michael A Province, Devin M Absher, Donna K Arnett, Jose M Ordovas
Postprandial lipemia (PPL), the increased plasma triglyceride (TG) concentration after consuming a high-fat meal, is an independent risk factor for cardiovascular disease (CVD). Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study (EWAS) on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study...
October 24, 2016: Journal of Lipid Research
L E Wilson, S Harlid, Z Xu, D P Sandler, J A Taylor
BACKGROUND/OBJECTIVES: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study. SUBJECTS/METHODS: The Sister Study is a cohort of 50 884 U.S. women who had a sister with breast cancer but were free of breast cancer themselves at enrollment...
October 24, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Corneille Edgar Ontsouka, Xiao Huang, Eldar Aliyev, Christiane Albrecht
Cell-based studies previously showed that the ATP-binding cassette transporter A1 (ABCA1) transfers cholesterol across mammary epithelial cells (MEC). Data for phospholipid transport are lacking, and it is unclear from which cellular source the transported cholesterol stems, whether this transport activates signaling pathways, and how lactogenic hormones regulate it. To clarify these aspects, lipid transport and expressional analyses were performed in bovine primary (bMEC) and/or immortalized (MAC-T) MEC cultures...
October 16, 2016: Molecular and Cellular Endocrinology
Kim V E Braun, Trudy Voortman, Klodian Dhana, Jenna Troup, Wichor M Bramer, John Troup, Rajiv Chowdhury, Abbas Dehghan, Taulant Muka, Oscar H Franco
Epigenetic mechanisms, including DNA methylation and histone modifications, might be involved in the regulation of blood lipid concentration variability and may thereby affect cardiovascular health. We aimed to systematically review studies investigating the association between epigenetic marks and plasma concentrations of triacylglycerol, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Six medical databases were searched until September 3rd 2015, reference lists were screened, and experts in the field were contacted...
October 13, 2016: Progress in Lipid Research
Tiantian Luo, Jing Hu, Dan Xi, Haowei Xiong, Wenshuai He, Jichen Liu, Menghao Li, Hao Lu, Jinzhen Zhao, Wenyan Lai, Zhigang Guo
Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4(+) T cells...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Blake J Cochran, Liming Hou, Anil Paul Chirackal Manavalan, Benjamin M Moore, Fatiha Tabet, Afroza Sultana, Luisa Cuesta Torres, Shudi Tang, Sudichhya Shrestha, Praween Senanayake, Mili Patel, William J Ryder, Andre Bongers, Marie Maraninchi, Valerie C Wasinger, Marit Westerterp, Alan R Tall, Philip J Barter, Kerry-Anne Rye
Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high glucose conditions and glucose disposal was shifted from skeletal muscle to adipose tissue...
October 4, 2016: Diabetes
Adam Ceroi, David Masson, Anne Roggy, Christophe Roumier, Cécile Chagué, Thierry Gauthier, Laure Philippe, Baptiste Lamarthée, Fanny Angelot-Delettre, Francis Bonnefoy, Sylvain Perruche, Sabeha Biichle, Claude Preudhomme, Elisabeth Macintyre, Laurent Lagrost, Francine Garnache-Ottou, Philippe Saas
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from plasmacytoid dendritic cells (PDC). No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared to those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDC. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes...
October 4, 2016: Blood
Fen Liu, Yi Wang, Jing Xu, Fangqiang Liu, Rongdang Hu, Hui Deng
INTRODUCTION: Cardiovascular diseases are positively correlated with periodontal disease. However, the molecular mechanisms linking atherosclerosis and periodontal infection are not clear. This study aimed to determine whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) altered the expression of genes regulating cholesterol metabolism in macrophages in the presence of low-density lipoprotein (LDL). MATERIAL AND METHODS: THP-1-derived macrophages were exposed to different concentrations (0...
October 1, 2016: Archives of Medical Science: AMS
Amanda Karolina Soares E Silva, Fabiana Oliveira Dos Santos Gomes, Bruna Dos Santos Silva, Edlene Lima Ribeiro, Amanda Costa Oliveira, Shyrlene Meyre da Rocha Araújo, Ingrid Tavares de Lima, Anne Gabrielle Vasconcelos Oliveira, Martina Rudnicki, Dulcineia S P Abdalla, Maria do Carmo Alves de Lima, Ivan da Rocha Pitta, Christina Alves Peixoto
BACKGROUND: Atherosclerosis is a complex disorder with a multifactorial pathogenesis. We previously indicated that the new TZD LPSF/GQ-02 inhibits hepatic steatosis and inflammation, which are reported as risk factors for atherosclerosis development. Here, we explored the effects of LPSF/GQ-02 on atherosclerosis in LDLr-/- mice comparing two treatment periods. METHODS AND RESULTS: LDLr(-/-) mice were fed a high-fat diet for 10 and 12 weeks and received oral treatment with LPSF/GQ-02 (30mg/kg/day) or pioglitazone (20mg/kg/day) for 15 and 30 days, respectively...
September 29, 2016: European Journal of Pharmacology
Lei Xu, Yi-Ru Wang, Pei-Cheng Li, Bo Feng
BACKGROUND: Previous reports have suggested that advanced glycation end products (AGEs) participate in the pathogenesis of diabetic macroangiopathy. Our previous study have found that AGEs can increase the lipid droplets accumulation in aortas of diabetic rats, but the current understanding of the mechanisms remains incomplete by which AGEs affect lipids accumulation in macrophages and accelerate atherosclerosis. In this study, we investigated the role of AGEs on lipids accumulation in macrophages and the possible molecular mechanisms including cholesterol influx, esterification and efflux of macrophages...
2016: Lipids in Health and Disease
S Sayols-Baixeras, I Subirana, C Lluis-Ganella, F Civeira, J Roquer, A N Do, D Absher, D Muñoz, C Soriano-Tárraga, J Jiménez-Conde, J Ordovas, M Senti, S Aslibekyan, J Marrugat, D K Arnett, R Elosua
Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n=645) and validation in the Framingham Offspring Study (n=2,542)...
September 15, 2016: Human Molecular Genetics
Emilie Crouchet, Mathieu Lefèvre, Eloi R Verrier, Marine A Oudot, Thomas F Baumert, Catherine Schuster
OBJECTIVE: The HCV life cycle and the lipid metabolism are inextricably intertwined. In the blood, HCV virions are associated with lipoproteins, forming lipoviroparticles (LVPs), which are the most infectious form of the virus. Apolipoprotein E (apoE), a key LVP component, plays an essential role in HCV entry, assembly and egress. ApoE is also a cell host factor involved in lipoprotein homeostasis. Although the majority of apoE is associated with lipoproteins, a lipid-free (LF) form exists in blood...
September 8, 2016: Gut
María E Fernández-Suárez, Joan C Escolà-Gil, Oscar Pastor, Alberto Dávalos, Francisco Blanco-Vaca, Miguel A Lasunción, Javier Martínez-Botas, Diego Gómez-Coronado
Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression...
2016: Scientific Reports
Gamze Guney Eskiler, Gulsah Cecener, Berrin Tunca, Unal Egeli
The development of resistance to tamoxifen (Tam) remains a challenging clinical problem for ER+ breast cancer patients. To understand the mechanisms underlying of resistance, previous studies have driven the acquisition of Tam resistance by exposing cells to varying concentration of drug for varying lengths of time. However, a detailed protocol for the establishment of Tam-resistant cells remains to be clarified. In the present study, we aimed to determine and compare the effect of different in vitro protocols on the degree of resistance to 4-hydroxytamoxifen (4-OH Tam) for MCF7 cells...
September 1, 2016: Cell Biology and Toxicology
Hong Lu, Yongyu Xu, Feng Cui
The ATP-binding cassette (ABC) transporter family functions in the ATP-dependent transportation of various substrates across biological membranes. ABC proteins participate in various biological processes and insecticide resistance in insects, and are divided into eight subfamilies (A-H). Mosquitoes are important vectors of human diseases, but the mechanism by which the ABC transporter family evolves in mosquitoes is unknown. In this study, we classified and compared the ABC transporter families of three mosquitoes, namely, Anopheles gambiae, Aedes aegypti, and Culex pipiens quinquefasciatus...
September 2016: Pesticide Biochemistry and Physiology
Claudia Lanterna, Andrea Musumeci, Laura Raccosta, Gianfranca Corna, Marta Moresco, Daniela Maggioni, Raffaella Fontana, Claudio Doglioni, Claudio Bordignon, Catia Traversari, Vincenzo Russo
Tumor-derived metabolites dampen tumor-infiltrating immune cells and antitumor immune responses. Among the various metabolites produced by tumors, we recently showed that cholesterol oxidized products, namely oxysterols, favor tumor growth through the inhibition of DC migration toward lymphoid organs and by promoting the recruitment of pro-tumor neutrophils within the tumor microenvironment. Here, we tested different drugs capable of blocking cholesterol/oxysterol formation. In particular, we tested efficacy and safety of different administration schedules, and of immunotherapy-based combination of a class of compounds, namely zaragozic acids, which inhibit cholesterol pathway downstream of mevalonate formation, thus leaving intact the formation of the isoprenoids, which are required for the maturation of proteins involved in the immune cell function...
August 12, 2016: Cancer Immunology, Immunotherapy: CII
Hui Gao, Lingyan Li, Lan Li, Bo Gong, Pengzhi Dong, Patrick Asare Fordjour, Yan Zhu, Guanwei Fan
Contemporary research suggests that macrophage foam cell and cholesterol efflux defect play pivotal role in atherogenesis. We reported on the heretofore unknown therapeutic effect of Danshensu (DSS) in reducing intracellular cholesterol level and unraveled the mechanism of DSS promotes cholesterol efflux. Oxidized low-density lipoprotein stimulation of Raw264.7 cells into foam cells, which were treated with DSS and co-treated with Simvastatin and Rosiglitazone. PPARγ, ABCA1, ABCG1, SR-BI, CD36, and LXR-α mRNA were quantified by Real-Time PCR...
September 2016: Lipids
Jie Wang, Mei-Jun Feng, Rui Zhang, De-Min Yu, Sai-Jun Zhou, Rui Chen, Pei Yu
Oxidized low-density lipoprotein (oxLDL) can bind to β2-glycoprotein I (β2GPI) and C-reactive protein (CRP) to form stable complexes, which exert certain effects in diabetic cardiovascular disease. A previous study by our group has confirmed that the resulting complexes promote atherosclerosis in diabetic BALB/c mice. The present study was designed to investigate the effects and potential mechanisms of oxLDL complexes on lipid accumulation and inflammatory reactions in RAW264.7 macrophages cultured in a hyperglycemic environment...
October 2016: Molecular Medicine Reports
Lihua Lai, Kathleen M Azzam, Wan-Chi Lin, Prashant Rai, Julie M Lowe, Kristin A Gabor, Jennifer H Madenspacher, Jim J Aloor, John S Parks, Anders M Näär, Michael B Fessler
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by promoting degradation and/or repressing translation of specific target mRNAs. Several miRNAs have been identified that regulate the amplitude of the innate immune response by directly targeting Toll-like receptor (TLR) pathway members and/or cytokines. miR-33a and miR-33b (the latter present in primates but absent in rodents and lower species) are located in introns of the sterol regulatory element-binding protein (SREBP)-encoding genes and control cholesterol/lipid homeostasis in concert with their host gene products...
September 9, 2016: Journal of Biological Chemistry
Yuzhou Gui, Sheng Yao, Hong Yan, Liang Hu, Chengyin Yu, Fei Gao, Cong Xi, Huihui Li, Yang Ye, Yiping Wang
AIMS: Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. We hypothesized that nagilactone B (NLB), a small molecule extracted from the root bark of Podocarpus nagi (Podocarpaceae), suppresses atherosclerosis in an atherosclerotic mouse model. METHODS AND RESULTS: Male apoE-deficient mice on C57BL/6J background received NLB (10 and 30 mg/kg) for 12 weeks. Compared with the model group, NLB treatment (10 and 30 mg/kg) significantly reduced en face lesions of total aorta areas...
October 2016: Cardiovascular Research
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