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https://www.readbyqxmd.com/read/27996196/reverse-translational-study-of-fenofibrate-s-observed-effects-in-diabetes-associated-retinopathy
#1
R A Farris, E T Price
Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA...
December 20, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27995417/high-density-lipoprotein-from-subjects-with-coronary-artery-disease-promotes-macrophage-foam-cell-formation-role-of-scavenger-receptor-cd36-and-erk-mapk-signaling
#2
S Sini, D Deepa, S Harikrishnan, N Jayakumari
Although high-density lipoprotein is atheroprotective, it can become dysfunctional in chronic inflammatory conditions and increase cardiovascular risk. We previously demonstrated that HDL from subjects with documented coronary artery disease is dysfunctional and is pro-oxidant/proinflammatory in macrophages. Here we examined the influence of dysfunctional/proinflammatory HDL (piHDL) on lipid accumulation in human macrophages, in comparison to functional HDL (nHDL). Exposure of macrophages to piHDL, in contrast to nHDL, resulted in oxidative stress and marked uptake of lipids from piHDL, leading to the formation of foam cell phenotype as noted by oil red O staining with concomitant increase in total cellular cholesterol content...
December 19, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27994765/discovery-of-highly-potent-liver-x-receptor-%C3%AE-agonists
#3
Ellen K Kick, Brett B Busch, Richard Martin, William C Stevens, Venkataiah Bollu, Yinong Xie, Brant C Boren, Michael C Nyman, Max H Nanao, Lam Nguyen, Artur Plonowski, Ira G Schulman, Grace Yan, Huiping Zhang, Xiaoping Hou, Meriah N Valente, Rangaraj Narayanan, Kamelia Behnia, A David Rodrigues, Barry Brock, James Smalley, Glenn H Cantor, John Lupisella, Paul Sleph, Denise Grimm, Jacek Ostrowski, Ruth R Wexler, Todd Kirchgessner, Raju Mohan
Introducing a uniquely substituted phenyl sulfone into a series of biphenyl imidazole liver X receptor (LXR) agonists afforded a dramatic potency improvement for induction of ATP binding cassette transporters, ABCA1 and ABCG1, in human whole blood. The agonist series demonstrated robust LXRβ activity (>70%) with low partial LXRα agonist activity (<25%) in cell assays, providing a window between desired blood cell ABCG1 gene induction in cynomolgus monkeys and modest elevation of plasma triglycerides for agonist 15...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27989886/intracoronary-imaging-cholesterol-efflux-and-transcriptomes-after-intensive-statin-treatment-the-yellow-ii-study
#4
Annapoorna S Kini, Yuliya Vengrenyuk, Khader Shameer, Akiko Maehara, Meerarani Purushothaman, Takahiro Yoshimura, Mitsuaki Matsumura, Melissa Aquino, Nezam Haider, Kipp W Johnson, Ben Readhead, Brian A Kidd, Jonathan E Feig, Prakash Krishnan, Joseph Sweeny, Milind Mahajan, Pedro Moreno, Roxana Mehran, Jason C Kovacic, Usman Baber, Joel T Dudley, Jagat Narula, Samin Sharma
BACKGROUND: Despite the extensive evidence for the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects in remain elusive. OBJECTIVES: To assess the changes in plaque morphology by intravascular imaging with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cells (PBMC) transcriptomics in patients receiving high-dose statin therapy. METHODS: In a prospective study, 85 patients with stable multivessel coronary artery disease underwent percutaneous coronary intervention for a culprit lesion followed by intracoronary multi-modality imaging including optical coherence tomography (OCT) of an obstructive non-culprit lesion (NCL)...
October 27, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27980243/analysis-of-serum-cholesterol-efflux-capacity-in-a-minipig-model-of-nonischemic-heart-failure
#5
Federico Bigazzi, Maria Pia Adorni, Mariarita Puntoni, Francesco Sbrana, Vincenzo Lionetti, Beatrice Dal Pino, Elda Favari, Fabio A Recchia, Franco Bernini, Tiziana Sampietro
AIM: Circulating levels of high-density lipoprotein cholesterol (HDL-C) are decreased in patients with heart failure (HF). We tested whether HDL-C serum levels are associated with cardiac contractile dysfunction in a minipig HF model. METHODS: Blood samples were collected from 13 adult male minipigs: 1) before pacemaker implantation, 2) 10 days after surgery, and 3) 3 weeks after high-rate LV pacing. Serum cholesterol efflux capacity (CEC), an index of HDL functionality, was assessed through four mechanisms: ATP Binding Cassette transporter A1 (ABCA1), ATP Binding Cassette transporter G1 (ABCG1), Scavenger Receptor-Class B Type I (SR-BI) and Passive Diffusion (PD)...
December 15, 2016: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/27968834/methylation-loci-associated-with-body-mass-index-waist-circumference-and-waist-to-hip-ratio-in-chinese-adults-an-epigenome-wide-analysis
#6
Biqi Wang, Wenjing Gao, Jun Li, Canqing Yu, Weihua Cao, Jun Lv, Zengchang Pang, Liming Cong, Hua Wang, Xianping Wu, Liming Liang, Tangchun Wu, Liming Li
BACKGROUND: DNA methylation has been implicated in the pathology of obesity, but little is known about such epigenetic variants in Chinese people. We conducted an epigenome-wide analysis of methylation at CpG sites in relation to body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) among Chinese adult populations. METHODS: 469 twins from the Chinese National Twin Registry were the discovery cohort. After quality control, methylation levels in whole blood leukocyte DNA were tested for association with BMI, WC, and WHR using mixed linear regressions, adjusting for demographics, lifestyle, and family structure...
October 2016: Lancet
https://www.readbyqxmd.com/read/27940374/inhibitory-effect-of-pcsk9-on-abca1-protein-expression-and-cholesterol-efflux-in-macrophages
#7
Maria Pia Adorni, Eleonora Cipollari, Elda Favari, Ilaria Zanotti, Francesca Zimetti, Alberto Corsini, Chiara Ricci, Franco Bernini, Nicola Ferri
BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) may have extra-hepatic effects on cholesterol homeostasis of vascular macrophages. In this study, we aimed to investigate PCSK9 role on the anti-atherogenic process of ATP binding cassette transporter A1 (Abca1)-mediated cholesterol efflux. METHODS: Abca1-mediated cholesterol efflux was evaluated by a radioisotopic technique in mouse peritoneal macrophages (MPM) from wild-type (WT) or LDL receptor knock-out (Ldlr(-/-)) mice exposed to human recombinant PCSK9, in the presence of liver X receptor/retinoid X receptor (LXR/RXR) ligands or acetylated LDL (AcLDL) to stimulate Abca1 expression...
November 16, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27890613/activation-of-ppar%C3%AE-does-not-contribute-to-macrophage-abca1-expression-and-abca1-mediated-cholesterol-efflux-to-apoai
#8
Meixiu Jiang, Xiaoju Li
Activation of macrophage ABCA1/G1 expression and cholesterol efflux is believed one of the mechanisms by which PPARγ inhibits atherosclerosis. PPARγ can also activate CD36 expression, a receptor for oxLDL, which may supply LXR ligands to activate LXR-ABCA1/G1 pathways. However, the controversial effects of PPARγ on ABCA1 expression have been reported. In this study, we used peritoneal macrophages isolated from wild type and CD36 deficient (CD36(-/-)) mice to clarify if PPARγ ligands can influence ABCA1 expression by CD36 function...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27889764/high-uric-acid-activates-the-ros-ampk-pathway-impairs-cd68-expression-and-inhibits-oxldl-induced-foam-cell-formation-in-a-human-monocytic-cell-line-thp-1
#9
Chaohuan Luo, Xueke Lian, Liangli Hong, Jingfang Zou, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Yaqiu Hu, Huier Yuan, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Ichiro Hisatome, Tetsuya Yamamoto, Jiexiong Huang, Jidong Cheng
BACKGROUND/AIMS: Hyperuricemia is part of the metabolic-syndrome cluster of abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia, and hypertension. Monocytes/macrophages are critical in the development of metabolic syndrome, including gout, obesity and atherosclerosis. However, how high uric acid (HUA) exposure affects monocyte/macrophage function remains unclear. In this study, we investigated the molecular mechanism of HUA exposure in monocytes/macrophages and its impact on oxidized low-density lipoprotein (oxLDL)-induced foam-cell formation in a human monocytic cell line, THP-1...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27862930/piperine-inhibits-abca1-degradation-and-promotes-cholesterol-efflux-from-thp-1-derived-macrophages
#10
Limei Wang, Veronika Palme, Susanne Rotter, Nicole Schilcher, Malsor Cukaj, Dongdong Wang, Angela Ladurner, Elke H Heiss, Herbert Stangl, Verena M Dirsch, Atanas G Atanasov
SCOPE: Increased macrophage cholesterol efflux (ChE) is considered to have anti-atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a ChE inducer in THP-1-derived macrophages, and mechanisms underlying this effect are explored. METHODS AND RESULTS: Without affecting cell viability, piperine concentration-dependently enhances ChE in THP-1-derived macrophages from 25 to 100 μM...
November 15, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27815075/gly-14-humanin-inhibits-ox-ldl-uptake-and-stimulates-cholesterol-efflux-in-macrophage-derived-foam-cells
#11
Wa-Wa Zhu, Shu-Rong Wang, Zhi-Hua Liu, Yong-Jun Cao, Fen Wang, Jing Wang, Chun-Feng Liu, Ying Xie, Ying Xie, Yan-Lin Zhang
Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264...
January 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27807703/the-critical-role-of-abcg1-and-ppar%C3%AE-lxr%C3%AE-signaling-in-tlr4-mediates-inflammatory-responses-and-lipid-accumulation-in-vascular-smooth-muscle-cells
#12
Xiaojie Cao, Lili Zhang, Chunhai Chen, Qingsong Wang, Lu Guo, Qinlong Ma, Ping Deng, Gang Zhu, Binghu Li, Yan Pi, Chunyan Long, Lei Zhang, Zhengping Yu, Zhou Zhou, Jingcheng Li
Toll-like receptor 4 (TLR4) plays critical roles in vascular inflammation, lipid accumulation and atherosclerosis development. However, the mechanisms underlying these processes are still not well established, especially in vascular smooth muscle cells (VSMCs). ATP-binding cassette transporter G1 (ABCG1) is one of the key genes mediating inflammation and cellular lipid accumulation. The function of TLR4 in regulating the expression of ABCG1 and the underlying molecular mechanisms remain to be elucidated. In this study, we cultured VSMCs from the thoracic aortas of mice and treated the cells with 50 μg/ml oxidized low-density lipoprotein (oxLDL) to activate TLR4 signaling...
November 2, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27787563/association-of-abcg1-with-neovascular-age-related-macular-degeneration-and-polypoidal-choroidal-vasculopathy-in-chinese-and-japanese
#13
Li Ma, Ke Liu, Motokazu Tsujikawa, Haoyu Chen, Marten E Brelen, Vesta C K Chan, Timothy Y Y Lai, Kaori Sayanagi, Chicako Hara, Noriyasu Hashida, Pancy O S Tam, Alvin L Young, Weiqi Chen, Kohji Nishida, Chi Pui Pang, Li Jia Chen
Purpose: We investigated the association of the ATP-binding cassette, subfamily G, member 1 (ABCG1) gene with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) in independent Chinese and Japanese cohorts. Methods: A total of 12 haplotype-tagging single-nucleotide polymorphisms (SNPs) and the SNP rs57137919 in the ABCG1 gene were first analyzed in a Hong Kong Chinese cohort of 235 nAMD, 236 PCV, and 365 controls, using TaqMan genotyping assays...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27777315/epigenome-wide-association-study-of-triglyceride-postprandial-responses-to-a-high-fat-dietary-challenge
#14
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, José M Ordovás
Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for 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 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...
December 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27773939/an-epigenome-wide-study-of-body-mass-index-and-dna-methylation-in-blood-using-participants-from-the-sister-study-cohort
#15
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 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment...
January 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27760380/in%C3%A2-vitro-characterization-and-endocrine-regulation-of-cholesterol-and-phospholipid-transport-in-the-mammary-gland
#16
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 17, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27746199/the-role-of-dna-methylation-in-dyslipidaemia-a-systematic-review
#17
REVIEW
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
https://www.readbyqxmd.com/read/27742830/lck-inhibits-heat-shock-protein-65-mediated-reverse-cholesterol-transport-in-t-cells
#18
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
https://www.readbyqxmd.com/read/27702832/impact-of-perturbed-pancreatic-%C3%AE-cell-cholesterol-homeostasis-on-adipose-tissue-and-skeletal-muscle-metabolism
#19
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...
December 2016: Diabetes
https://www.readbyqxmd.com/read/27702801/lxr-agonist-treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm-restores-cholesterol-efflux-and-triggers-apoptosis
#20
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 (PDC) neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from PDCs. 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 with those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDCs. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes...
December 8, 2016: Blood
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