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https://www.readbyqxmd.com/read/29774529/inhibition-of-prmt3-activity-selectively-impairs-lxr-driven-transcription-of-hepatic-lipogenic-genes-in-vivo
#1
Joya E Nahon, Christianne Groeneveldt, Janine J Geerling, Miranda Van Eck, Menno Hoekstra
BACKGROUND AND PURPOSE: Agonists for the liver X receptor (LXR) are considered promising therapeutic moieties in cholesterol-driven diseases by promoting cellular cholesterol efflux pathways. However, current clinical application of these agents is hampered by the concomitant LXR-induced activation of a lipogenic transcriptional network, leading to hepatic steatosis. Recent studies have suggested that protein arginine methyltransferase 3 (PRMT3) may act as a selective co-activator of LXR activity...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29772548/epigenetic-regulation-of-genes-involved-in-the-reverse-cholesterol-transport-through-interaction-with-mirnas
#2
Mohamed Zaiou, Bertrand Henri Rihn, Ahmed Bakillah
microRNAs (miRNAs) are a group of small non-coding RNA molecules known to regulate target genes at the post-transcriptional level. miRNAs are implicated in the regulation of multiple pathophysiological processes including dyslipidemia, a major risk factor for atherosclerosis. Emerging evidence suggests that miRNAs act as a novel class of epigenetic regulators of high-density lipoproteins cholesterol (HDL-C) from synthesis to clearance contributing remarkably to the pathogenesis of atherosclerosis. Accumulating studies have revealed that miRNAs such as miR-33, miR-27, miR-144, miR-758 and miR-20 are involved in the post-transcriptional control of ABCA1, ABCG1 and SCARB1 genes regulatory network of the reverse cholesterol transport (RCT)...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29751497/epigenetic-regulation-of-atp-binding-cassette-protein-a1-abca1-gene-expression-a-new-era-to-alleviate-atherosclerotic-cardiovascular-disease
#3
Mohamed Zaiou, Ahmed Bakillah
The most important function of high density lipoprotein (HDL) is its ability to remove cholesterol from cells and tissues involved in the early stages of atherosclerosis back to the liver for excretion. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the major part of cholesterol efflux to HDL in macrophage foam cells. Thus, promoting the process of reverse cholesterol transport (RCT) by upregulating mainly ABCA1 remains one of the potential targets for the development of new therapeutic agents against atherosclerosis...
May 3, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29743204/apoe-isoforms-and-carboxyl-terminal-truncated-apoe4-forms-affect-neuronal-bace1-levels-and-a%C3%AE-production-independently-of-their-cholesterol-efflux-capacity
#4
Ioannis Dafnis, Christina Raftopoulou, Christina Mountaki, Evgenia Megalou, Vassilis I Zannis, Angeliki Chroni
The beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates the production of amyloid-beta peptide (Aβ) which is central to the pathogenesis of Alzheimer's disease (AD). Changes in brain cholesterol homeostasis have been suggested to affect Aβ metabolism. Cholesterol homeostasis is maintained in the brain by apolipoprotein E (apoE). The apoE4 isoform constitutes the major risk factor for AD. Here, we investigated the effect of apoE forms on Aβ generation and on BACE1 levels. We also examined the potential involvement in these processes of cholesterol transporters ABCG1 and ABCG4 or the lipoprotein receptor SR-BI that are implicated in cholesterol efflux to apoE...
May 9, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29713043/epigenome-wide-association-study-of-adiposity-and-future-risk-of-obesity-related-diseases
#5
Gianluca Campanella, Marc J Gunter, Silvia Polidoro, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Giovanni Fiorito, Simonetta Guarrera, Licia Iacoviello, Ingvar A Bergdahl, Beatrice Melin, Per Lenner, Theo M C M de Kok, Panagiotis Georgiadis, Jos C S Kleinjans, Soterios A Kyrtopoulos, H Bas Bueno-de-Mesquita, Karen A Lillycrop, Anne M May, N Charlotte Onland-Moret, Robert Murray, Elio Riboli, Monique Verschuren, Eiliv Lund, Nicolle Mode, Torkjel M Sandanger, Valentina Fiano, Morena Trevisan, Giuseppe Matullo, Philippe Froguel, Paul Elliott, Paolo Vineis, Marc Chadeau-Hyam
BACKGROUND: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction. METHODS: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29710032/effects-of-chronic-whey-protein-supplementation-on-atherosclerosis-in-apoe-mice
#6
Zheng Zhang, Ru Zhang, Zhi-Zhen Qin, Jia-Ping Chen, Jia-Ying Xu, Li-Qiang Qin
Whey protein is associated with improvement of metabolic syndrome. This study aimed to evaluate effects of whey protein on atherosclerosis in ApoE-/- mice. Male ApoE-/- mice were fed with a high-fat/cholesterol diet (HFCD), or HFCD supplemented with 10% or 20% whey protein for 18 wk. At the end of experiment, serum lipid profiles and inflammatory cytokines were assayed. Livers were examined using HE staining and Oil Red O staining. Aortas were used for en face and cryosection analyses to observe aortic lesions...
2018: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/29695588/mindin-deficiency-in-macrophages-protects-against-foam-cell-formation-and-atherosclerosis-by-targeting-lxr-%C3%AE
#7
Cheng Zhang, Juan-Juan Qin, Fu-Han Gong, Jing-Jing Tong, Wen-Lin Cheng, Haiping Wang, Yan Zhang, Xueyong Zhu, Zhi-Gang She, Hao Xia, Li-Hua Zhu
Abstract Background - Mindin, which is a highly conserved ECM protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes and immune responses. The aim of this study was to assess whether mindin contributes to the development of atherosclerosis. Methods and Results - A significant upregulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE-/-  mice after HFD treatment. Mindin-/- ApoE-/- mice and macrophage-specific mindin overexpression in ApoE-/- mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis...
April 25, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29678642/heat-shock-protein-70-accelerates-atherosclerosis-by-downregulating-the-expression-of-abca1-and-abcg1-through-the-jnk-elk-1-pathway
#8
Zhen-Wang Zhao, Min Zhang, Ling-Yan Chen, Duo Gong, Xiao-Dan Xia, Xiao-Hua Yu, Si-Qi Wang, Xiang Ou, Xiao-Yan Dai, Xi-Long Zheng, Da-Wei Zhang, Chao-Ke Tang
BACKGROUND AND AIMS: Recent studies have suggested that heat shock protein 70 (HSP70) may play critical roles in cardiovascular disease. However, the effects of HSP70 on the development of atherosclerosis in apoE-/- mice remain largely unknown. This study was to investigate the role and potential mechanism of HSP70 in atherosclerosis. METHODS: HSP70 was overexpressed in apoE-/- mice and THP-1-derived macrophages with lentiviral vectors. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaque in apoE-/- mice fed the Western type diet...
April 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29670629/regulation-of-human-%C3%AE-%C3%AE-t-cells-by-btn3a1-protein-stability-and-atp-binding-cassette-transporters
#9
David A Rhodes, Hung-Chang Chen, James C Williamson, Alfred Hill, Jack Yuan, Sam Smith, Harriet Rhodes, John Trowsdale, Paul J Lehner, Thomas Herrmann, Matthias Eberl
Activation of human Vγ9/Vδ2 T cells by "phosphoantigens" (pAg), the microbial metabolite ( E )-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670126/temporary-sequestration-of-cholesterol-and-phosphatidylcholine-within-extracellular-domains-of-abca1-during-nascent-hdl-generation
#10
Masato Ishigami, Fumihiko Ogasawara, Kohjiro Nagao, Hidehiko Hashimoto, Yasuhisa Kimura, Noriyuki Kioka, Kazumitsu Ueda
The quality and quantity of high-density lipoprotein (HDL) in blood plasma are important for preventing coronary artery disease. ATP-binding cassette protein A1 (ABCA1) and apolipoprotein A-I (apoA-I) play essential roles in nascent HDL formation, but controversy persists regarding the mechanism by which nascent HDL is generated. In the "direct loading model", apoA-I acquires lipids directly from ABCA1 while it is bound to the transporter. By contrast, in the "indirect model", apoA-I acquires lipids from the specific membrane domains created by ABCA1...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29643945/epigenome-wide-association-study-of-metabolic-syndrome-in-african-american-adults
#11
Tomi Akinyemiju, Anh N Do, Amit Patki, Stella Aslibekyan, Degui Zhi, Bertha Hidalgo, Hemant K Tiwari, Devin Absher, Xin Geng, Donna K Arnett, Marguerite R Irvin
Background: The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29605604/effects-of-rosuvastatin-on-the-expression-of-the-genes-involved-in-cholesterol-metabolism-in-rat-adaptive-responses-by-extrahepatic-tissues
#12
Yasin Ahmadi, Amir Ghorbani Haghjoo, Siavoush Dastmalchi, Mahboob Nemati, Nasrin Bargahi
BACKGROUND: Statins mostly target the liver; therefore, increase in the synthesis of cholesterol by extra-hepatic tissues and then transferring this cholesterol to the liver can be regarded as adaptive responses by these tissues. In addition to cholesterol, these adaptive responses can increase isoprenoid units as byproducts of the cholesterol biosynthesis pathway; isoprenoids play a key role in regulating cell signaling pathways and cancer development. Thus, there is a primary need for in vivo investigation of the effects of statins on the cholesterol metabolism in the extra-hepatic tissues...
March 29, 2018: Gene
https://www.readbyqxmd.com/read/29599133/lal-lysosomal-acid-lipase-promotes-reverse-cholesterol-transport-in-vitro-and-in-vivo
#13
Kristin L Bowden, Joshua A Dubland, Teddy Chan, You-Hai Xu, Gregory A Grabowski, Hong Du, Gordon A Francis
OBJECTIVE: To explore the role of LAL (lysosomal acid lipase) in macrophage cholesterol efflux and whole-body reverse cholesterol transport. APPROACH AND RESULTS: Immortalized peritoneal macrophages from lal-/ - mice showed reduced expression of ABCA1 (ATP-binding cassette transporter A1) and ABCG1 (ATP-binding cassette transporter G1), reduced production of the regulatory oxysterol 27-hydroxycholesterol, and impaired suppression of cholesterol synthesis on exposure to acetylated low-density lipoprotein when compared with lal+/+ macrophages...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29580474/transport-of-cowpea-bean-derived-peptides-and-their-modulator-effects-on-mrna-expression-of-cholesterol-related-genes-in-caco-2-and-hepg2-cells
#14
Marcelo Rodrigues Marques, Alvaro Cerda, Gustavo Guadagnucci Fontanari, Daniel Carvalho Pimenta, Rosana Manólio Soares-Freitas, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata, José Alfredo Gomes Arêas
This work studied the cell transport of peptidase-generated peptides from cowpea bean proteins and their effects on mRNA expression of cholesterol-related genes in intestinal and liver cells. The ≤3 kDa hydrolysate was obtained and incubated with Caco-2 intestinal cells using Transwell® plates. HepG2 liver cells were incubated with synthetic analogues of peptides (MELNAVSVVHS and MELNAVSVVSH) identified by "de novo" peptide sequencing in the Caco-2 monolayer permeates. The mRNA expression of NPC1L1, ABCA1 and ABCG1 was measured in Caco-2 cells, in the presence or absence of ≤3 kDa hydrolysate and the expression of HMGCR, SREBP2, LXRα, AMPK1, was determined in the HepG2 cells in the presence or absence of synthetic peptides...
May 2018: Food Research International
https://www.readbyqxmd.com/read/29574773/omega-3-fatty-acids-modulate-the-lipid-profile-membrane-architecture-and-gene-expression-of-leiomyoma-cells
#15
Md Soriful Islam, Clara Castellucci, Rosamaria Fiorini, Stefania Greco, Riccardo Gagliardi, Alessandro Zannotti, Stefano R Giannubilo, Andrea Ciavattini, Natale G Frega, Deborah Pacetti, Pasquapina Ciarmela
Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega-3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin β1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells...
March 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29567540/silencing-zap70-prevents-hsp65-induced-reverse-cholesterol-transport-and-nf-%C3%AE%C2%BAb-activation-in-t-cells
#16
Jing Hu, Tiantian Luo, Dan Xi, Kai Guo, Lu Hu, Jinzhen Zhao, Si Chen, Zhigang Guo
T cell activation by antigens binding to the T cell receptor (TCR) must be properly regulated to ensure normal T cell development. The ζ chain-associated 70-kDa protein (ZAP70) is sequentially activated in response to TCR engagement and serves as a critical component of the TCR signaling pathway, which is essential for T cell activation. However, some roles of ZAP70 have not been fully elucidated. In the present study, we analyzed the effects of ZAP70 on the cholesterol efflux rate, nuclear factor κB (NF-κB) activation and cell proliferation in T cells...
March 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29540530/control-of-insulin-granule-formation-and-function-by-the-abc-transporters-abcg1-and-abca1-and-by-oxysterol-binding-protein-osbp
#17
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
https://www.readbyqxmd.com/read/29533793/silica-nanoparticles-promote-oxldl-induced-macrophage-lipid-accumulation-and-apoptosis-via-endoplasmic-reticulum-stress-signaling
#18
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
https://www.readbyqxmd.com/read/29524862/interleukin-32-upregulates-the-expression-of-abca1-and-abcg1-resulting-in-reduced-intracellular-lipid-concentrations-in-primary-human-hepatocytes
#19
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
https://www.readbyqxmd.com/read/29505925/dihydromyricetin-ameliorates-foam-cell-formation-via-lxr%C3%AE-abca1-abcg1-dependent-cholesterol-efflux-in-macrophages
#20
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...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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