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https://www.readbyqxmd.com/read/28634189/reduced-platelet-count-but-no-major-platelet-function-abnormalities-are-associated-with-loss-of-function-atp-binding-cassette-1-abca1-gene-mutations
#1
Pietro Minuz, Alessandra Meneguzzi, Eti Alessandra Femia, Cristiano Fava, Stefano Calabria, Mariangela Scavone, Donatella Benati, Giovanni Poli, Carlo Zancanaro, Sebastiano Calandra, Tiziano Lucchi, Marco Cattaneo
Loss of function mutations of the the ATP-binding cassette-1 (ABCA1) gene are the cause of Tangier disease (TD) in homozygous subjects and familial HDL deficiency (FHD) in heterozygous subjects. These disorders are characterized by reduced plasma HDL-cholesterol and altered efflux of cholesterol from cells. Previous studies in TD patients and ABCA1(-/-) murine models reported defects in platelet count, morphology and function, but the issue is still controversial. We analysed three subjects with low to very low HDL cholesterol levels due to loss of function mutations of the ABCA1 gene...
June 20, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28630870/placental-abca1-expression-is-increased-in-spontaneous-preterm-deliveries-compared-with-iatrogenic-preterm-deliveries-and-term-deliveries
#2
Xie Cheng-Mao, Long Yan, Lin Li, Jin Hua, Wang Xiao-Ju, Zhang Jie-Wen
OBJECTIVE: Abnormal expression of ABCA1 and ABCG1 in the placenta can elicit lipid metabolism disorder and adverse pregnancy outcomes. However, whether it is associated with preterm delivery remains unclear. Our present study aimed to evaluate the relationship between abnormal expression of ABCA1 or ABCG1 and preterm delivery. METHODS: Maternal blood and placental tissues from women with spontaneous deliveries (SPD), iatrogenic deliveries (IPD), and term deliveries (TD) were collected...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28625343/short-term-cooling-increases-serum-triglycerides-and-small-high-density-lipoprotein-levels-in-humans
#3
Geerte Hoeke, Kimberly J Nahon, Leontine E H Bakker, Sabine S C Norkauer, Donna L M Dinnes, Maaike Kockx, Laeticia Lichtenstein, Diana Drettwan, Anne Reifel-Miller, Tamer Coskun, Philipp Pagel, Fred P H T M Romijn, Christa M Cobbaert, Ingrid M Jazet, Laurent O Martinez, Leonard Kritharides, Jimmy F P Berbée, Mariëtte R Boon, Patrick C N Rensen
BACKGROUND: Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase-mediated catabolism of triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. OBJECTIVE: The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men...
May 3, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28611100/ampk-activation-enhances-the-anti-atherogenic-effects-of-high-density-lipoproteins-in-apoe-mice
#4
Ang Ma, Jing Wang, Liu Yang, Yuanyuan An, Haibo Zhu
HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE-/-) mice fed with a high fat diet. After administration, although there no changes in serum lipid levels among the groups...
June 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28610841/hsp27-promotes-abca1-expression-and-cholesterol-efflux-through-the-pi3k-pkc%C3%AE-sp1-pathway-in-thp-1-macrophages
#5
Hai-Jun Kuang, Guo-Jun Zhao, Wu-Jun Chen, Min Zhang, Gao-Feng Zeng, Xi-Long Zheng, Chao-Ke Tang
Heat shock protein 27 (Hsp27) is a putative biomarker and therapeutic target in atherosclerosis. This study was to explore the potential mechanisms underlying Hsp27 effects on ATP-binding cassette transporter A1 (ABCA1) expression and cellular cholesterol efflux. THP-1 macrophage-derived foam cells were infected with adenovirus to express wild-type Hsp27, hyper-phosphorylated Hsp27 mimic (3D Hsp27), antisense Hsp27 or hypo-phosphorylated Hsp27 mimic (3A Hsp27). Wild-type and 3D Hsp27 were found to up-regulate ABCA1 mRNA and protein expression and increase cholesterol efflux from cells...
June 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28607931/genetic-epidemiology-of-type-2-diabetes-in-mexican-mestizos
#6
REVIEW
Eiralí Guadalupe García-Chapa, Evelia Leal-Ugarte, Valeria Peralta-Leal, Jorge Durán-González, Juan Pablo Meza-Espinoza
There are currently about 415 million people with diabetes worldwide, a figure likely to increase to 642 million by 2040. In 2015, Mexico was the second Latin American country and sixth in the world in prevalence of this disorder with nearly 11.5 million of patients. Type 2 diabetes (T2D) is the main kind of diabetes and its etiology is complex with environmental and genetic factors involved. Indeed, polymorphisms in several genes have been associated with this disease worldwide. To estimate the genetic epidemiology of T2D in Mexican mestizos a systematic bibliographic search of published articles through PubMed, Scopus, Google Scholar, and Web of Science was conducted...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28602962/microrna-20a-b-regulates-cholesterol-efflux-through-post-transcriptional-repression-of-atp-binding-cassette-transporter-a1
#7
Bin Liang, Xin Wang, Xiaosu Song, Rui Bai, Huiyu Yang, Zhiming Yang, Chuanshi Xiao, Yunfei Bian
ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and exhibits anti-atherosclerosis effects. Some microRNAs (miRs) regulate ABCA1 expression, and recent studies have shown that miR-20a/b might play a critical role in atherosclerotic diseases. Here, we attempted to clarify the potential contribution of miR-20a/b in post-transcriptional regulation of ABCA1, cholesterol efflux, and atherosclerosis. We performed bioinformatics analysis and found that miR-20a/b was highly conserved and directly bound to ABCA1 mRNA with low binding free energy...
June 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28602350/structure-of-the-human-lipid-exporter-abca1
#8
Hongwu Qian, Xin Zhao, Pingping Cao, Jianlin Lei, Nieng Yan, Xin Gong
ABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of nascent high-density lipoprotein (HDL). Mutations of human ABCA1 are associated with Tangier disease and familial HDL deficiency. Here, we report the cryo-EM structure of human ABCA1 with nominal resolutions of 4.1 Å for the overall structure and 3.9 Å for the massive extracellular domain. The nucleotide-binding domains (NBDs) display a nucleotide-free state, while the two transmembrane domains (TMDs) contact each other through a narrow interface in the intracellular leaflet of the membrane...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28601639/tofacitinib-ameliorates-atherosclerosis-and-reduces-foam-cell-formation-in-apoe-deficient-mice
#9
Zaicun Wang, Shumei Wang, Zunzhe Wang, Tiantian Yun, Chenchen Wang, Huating Wang
Atherosclerosis is a chronic inflammatory cardiovascular disease with high mortality worldwide. Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. However, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of Tofacitinib on atherogenic diet (ATD)-induced atherosclerosis using apolipoprotein E deficient (apoE-/-) mice...
June 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28599304/hdl-cholesterol-concentration-in-pregnant-chinese-han-women-of-late-second-trimester-associated-with-genetic-variants-in-cetp-abca1-apoc3-and-galnt2
#10
Mingxuan Cui, Wei Li, Liangkun Ma, Fan Ping, Juntao Liu, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
OBJECTIVE: To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). METHODS: Seven single-nucleotide polymorphisms (rs3764261 in CETP, rs1532085 in LIPC, rs7241918 in LIPG, rs1883025 in ABCA1, rs4225 in APOC3, rs1059611 in LPL, and rs16851339 in GALNT2) were genotyped using the Sequenom MassArray system for 1,884 pregnant women...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596507/let-7g-suppresses-both-canonical-and-non-canonical-nf-%C3%AE%C2%BAb-pathways-in-macrophages-leading-to-anti-atherosclerosis
#11
Yung-Song Wang, Edward Hsi, Hsin-Yun Cheng, Shih-Hsien Hsu, Yi-Chu Liao, Suh-Hang H Juo
Transformation of macrophages to foam cells contributes to atherosclerosis. Here, we report that let-7g reduces macrophage transformation and alleviates foam cell apoptosis by suppressing both canonical and non-canonical NF-κB pathways. In the canonical pathway, let-7g inhibits phosphorylation of IKKβ and IκB, down-regulates SREBF2 and miR-33a, and up-regulates ABCA1. In the non-canonical pathway, let-7g directly knocks down MEKK1, IKKα and ablates IKKα phosphorylation. Let-7g's effects in macrophages can be almost completely blocked by inactivation of NF-κB signaling, which suggests that let-7g's effects are primarily mediated through the suppression of NF-κB pathways...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595267/cholesterol-uptake-and-regulation-in-high-grade-and-lethal-prostate-cancers
#12
Konrad H Stopsack, Travis A Gerke, Ove Andrén, Swen-Olof Andersson, Edward L Giovannucci, Lorelei A Mucci, Jennifer R Rider
Lethal prostate cancers have higher expression of squalene monooxygenase (SQLE), the second rate-limiting enzyme of cholesterol synthesis. Preclinical studies suggested that aberrant cholesterol regulators, receptors, and transporters contribute to cholesterol accumulation uniformly. We assessed their association with features of aggressive cancers. In the prospective prostate cancer cohorts within the Health Professional Follow-up Study, the Physicians' Health Study, and the Swedish Watchful Waiting Study, tumor mRNA expression profiling was performed...
June 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28595104/pre-%C3%AE-1-hdl-in-type-2-diabetes-mellitus
#13
S W Shiu, Y Wong, K C Tan
BACKGROUND AND AIMS: Pre-β1 HDL, being a major acceptor of free cholesterol from cells, plays an important role in reverse cholesterol transport. This study was performed to determine whether abnormalities in pre-β1 HDL concentration were present in type 2 diabetes irrespective of their HDL-cholesterol levels, and the impact on cholesterol efflux. METHODS: 640 type 2 diabetic patients with or without cardiovascular disease (CVD) and 360 non-diabetic controls matched for serum HDL-cholesterol levels were recruited...
May 25, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28594401/upconversion-nanoparticle-mediated-photodynamic-therapy-induces-autophagy-and-cholesterol-efflux-of-macrophage-derived-foam-cells-via-ros-generation
#14
Xiaobo B Han, Hongxia X Li, Yueqing Q Jiang, Hao Wang, Xuesong S Li, Jiayuan Y Kou, Yinghong H Zheng, Zhongni N Liu, Hong Li, Jing Li, Dou Dou, You Wang, Ye Tian, Liming M Yang
Macrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28591582/hepatocyte-abca1-deletion-impairs-liver-insulin-signaling-and-lipogenesis
#15
Chia-Chi C Key, Mingxia Liu, C Lisa Kurtz, Soonkyu Chung, Elena Boudyguina, Timothy A Dinh, Alexander Bashore, Peter E Phelan, Barry I Freedman, Timothy F Osborne, Xuewei Zhu, Lijun Ma, Praveen Sethupathy, Sudha B Biddinger, John S Parks
Plasma membrane (PM) free cholesterol (FC) is emerging as an important modulator of signal transduction. Here, we show that hepatocyte-specific knockout (HSKO) of the cellular FC exporter, ATP-binding cassette transporter A1 (ABCA1), leads to decreased PM FC content and defective trafficking of lysosomal FC to the PM. Compared with controls, chow-fed HSKO mice had reduced hepatic (1) insulin-stimulated Akt phosphorylation, (2) activation of the lipogenic transcription factor Sterol Regulatory Element Binding Protein (SREBP)-1c, and (3) lipogenic gene expression...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28587337/effect-of-adiponectin-on-macrophage-reverse-cholesterol-transport-in-adiponectin-mice-and-its-mechanism
#16
Yueru Wang, Xin Wang, Yingying Guo, Yunfei Bian, Rui Bai, Bin Liang, Chuanshi Xiao
The objective of the present study was to investigate the effect of adiponectin (APN) on macrophage reverse cholesterol transport (RCT) in adiponectin-/- knockout mice (APN-/-mice) and its possible anti-atherosclerotic mechanism. A total of 30 male APN-/-mice were randomly divided into the control group and four intervention groups. The intervention groups were treated with intraperitoneal injections of APN, at doses of 50, 150, 200 and 250 µg/(kg/day), respectively, for 4 weeks. The control group received normal saline...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28580927/the-atp-binding-cassette-transporter-a1-regulates-phosphoantigen-release-and-v%C3%AE-9v%C3%AE-2-t-cell-activation-by-dendritic-cells
#17
Barbara Castella, Joanna Kopecka, Patrizia Sciancalepore, Giorgia Mandili, Myriam Foglietta, Nico Mitro, Donatella Caruso, Francesco Novelli, Chiara Riganti, Massimo Massaia
Vγ9Vδ2 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce Vγ9Vδ2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA)...
June 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28579886/d-4f-decreases-the-expression-of-a%C3%AE-protein-through-up-regulating-long-non-coding-rna-sirt1-as-in-samp8-mice
#18
Xiao-Han Ding, Jie Han, Yuan Liu, Ying Jin, Ping Ye
Cholesterol plays key roles on (Aβ) metabolism and production. D-4F is the apolipoprotein A-I mimetic peptide which has been revealed a critical role in regulation cholesterol. We aimed at identifying the effects of D-4F on Aβ production in SAMP8 and the underlying mechanisms. METHODS: SAMP8 mice (n = 15) were randomized into three groups for treatment with D-4F given in drinking water: high-dose group (0.5 mg/ml), low-dose group (0.3 mg/ml) and control group (just drinking water)...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28576406/puerarin-promotes-abca1-mediated-cholesterol-efflux-and-decreases-cellular-lipid-accumulation-in-thp-1-macrophages
#19
Cong-Hui Li, Duo Gong, Ling-Yan Chen, Min Zhang, Xiao-Dan Xia, Hai-Peng Cheng, Chong Huang, Zhen-Wang Zhao, Xi-Long Zheng, Xiao-Er Tang, Chao-Ke Tang
It was reported that puerarin decreases the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and increases high-density lipoprotein cholesterol (HDL-C) level, but the underlying mechanism is unclear. This study was designed to determine whether puerarin decreased lipid accumulation via up-regulation of ABCA1-mediated cholesterol efflux in THP-1 macrophage-derived foam cells. Our results showed that puerarin significantly promoted the expression of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein via the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor-alpha (LXR-α) pathway and decreased cellular lipid accumulation in human THP-1 macrophage-derived foam cells...
May 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28572541/pulmonary-endothelial-cell-dna-methylation-signature-in-pulmonary-arterial-hypertension
#20
Aurélie Hautefort, Julie Chesné, Jens Preussner, Soni S Pullamsetti, Jorg Tost, Mario Looso, Fabrice Antigny, Barbara Girerd, Marianne Riou, Saadia Eddahibi, Jean-François Deleuze, Werner Seeger, Elie Fadel, Gerald Simonneau, David Montani, Marc Humbert, Frédéric Perros
Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation.DNA was extracted from cultured PEC from idiopathic PAH (n = 11), heritable PAH (n = 10) and controls (n = 18)...
May 19, 2017: Oncotarget
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