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https://www.readbyqxmd.com/read/28899694/anti-atherosclerotic-effect-of-hesperidin-in-ldlr-mice-and-its-possible-mechanism
#1
Ye-Zi Sun, Jian-Fei Chen, Li-Min Shen, Ji Zhou, Cui-Fang Wang
Hesperidin, a citrus bioflavonoid, exerts numerous pharmacological activities. However, its protective effect against atherosclerosis in vivo remains poorly understood. In the present study, we aimed to observe the effects of hesperidin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr(-/-)) mice. After 12 weeks of treatment, the animals were sacrificed. The blood samples were collected for further analysis. Mouse peritoneal macrophages were collected. Hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation, gene expressions were performed on liver and aorta samples...
September 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28894120/blood-triglyceride-levels-are-associated-with-dna-methylation-at-the-serine-metabolism-gene-phgdh
#2
Vinh Truong, Siying Huang, Jessica Dennis, Mathieu Lemire, Nora Zwingerman, Dylan Aïssi, Irfahan Kassam, Claire Perret, Philip Wells, Pierre-Emmanuel Morange, Michael Wilson, David-Alexandre Trégouët, France Gagnon
Efficient interventions to reduce blood triglycerides are few; newer and more tolerable intervention targets are needed. Understanding the molecular mechanisms underlying blood triglyceride levels variation is key to identifying new therapies. To explore the role of epigenetic mechanisms on triglyceride levels, a blood methylome scan was conducted in 199 individuals from 5 French-Canadian families ascertained on venous thromboembolism, and findings were replicated in 324 French unrelated patients with venous thromboembolism...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889112/interplay-between-cigarette-smoking-and%C3%A2-pulmonary-reverse-lipid-transport
#3
Éric Jubinville, Maude Talbot, Jean-Christophe Bérubé, Mélanie Hamel-Auger, Michaël Maranda-Robitaille, Marie-Josée Beaulieu, Sophie Aubin, Marie-Ève Paré, David G Kallend, Benoit Arsenault, Yohan Bossé, Mathieu C Morissette
Reverse lipid transport is critical to maintain homeostasis. Smoking causes lipid accumulation in macrophages, therefore suggesting suboptimal reverse lipid transport mechanisms. In this study, we investigated the interplay between smoking and reverse lipid transport and the consequences on smoking-induced lung and peripheral alterations.To investigate the relationship between smoking and reverse lipid transport, we used a clinical lung gene expression dataset and a mouse model of cigarette smoke exposure. We also used ApoA-1(-/-) mice, with reduced reverse lipid transport capacity, and a recombinant ApoA-1 Milano/phospholipid complex (MDCO-216) to boost reverse lipid transport...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28869506/critical-role-of-the-human-atp-binding-cassette-g1-transporter-in-cardiometabolic-diseases
#4
REVIEW
Lise M Hardy, Eric Frisdal, Wilfried Le Goff
ATP-binding cassette G1 (ABCG1) is a member of the large family of ABC transporters which are involved in the active transport of many amphiphilic and lipophilic molecules including lipids, drugs or endogenous metabolites. It is now well established that ABCG1 promotes the export of lipids, including cholesterol, phospholipids, sphingomyelin and oxysterols, and plays a key role in the maintenance of tissue lipid homeostasis. Although ABCG1 was initially proposed to mediate cholesterol efflux from macrophages and then to protect against atherosclerosis and cardiovascular diseases (CVD), it becomes now clear that ABCG1 exerts a larger spectrum of actions which are of major importance in cardiometabolic diseases (CMD)...
September 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28863273/2-3-4-5-tetrahydroxystilbene-2-0-%C3%AE-d-glycoside-attenuates-atherosclerosis-in-apolipoprotein-e-deficient-mice-role-of-reverse-cholesterol-transport
#5
Xuemeng Chen, Kun Tang, Yi Peng, Xiaole Xu
The aim of this study was to evaluate the potential effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on atherosclerotic plaque development in ApoE-/- mice, and explore the mechanisms involved. Our data showed that after eight weeks treatment, TSG ameliorated serum levels of total cholesterol, triglyceride and low density lipoprotein cholesterol and increased serum level of high density lipoprotein cholesterol in ApoE-/- mice. TSG suppressed hepatic steatosis, atherosclerotic lesion formation and macrophage foam cell formation in ApoE-/- mice...
September 1, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28830907/plasma-cholesterol-homeostasis-hdl-remodeling-and-function-during-the-acute-phase-reaction
#6
Francesca Zimetti, Stefano De Vuono, Monica Gomaraschi, Maria Pia Adorni, Elda Favari, Nicoletta Ronda, Maria Anastasia Ricci, Fabrizio Veglia, Laura Calabresi, Graziana Lupattelli
Acute phase reaction (APR) is a systemic inflammation triggered by several conditions associated with lipid profile alterations. We evaluated whether APR also associates with changes in cholesterol synthesis and absorption, HDL structure, composition and cholesterol efflux capacity (CEC). We analyzed 59 subjects with APR related to infections, oncologic causes or autoimmune diseases and 39 controls. We detected no difference in markers of cholesterol synthesis and absorption. Conversely, a significant reduction of LpA-I- and LpAI:AII-containing HDL (-28% and -44...
August 22, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28807695/doxorubicin-enhances-oxysterol-levels-resulting-in-a-lxr-mediated-upregulation-of-cardiac-cholesterol-transporters
#7
Judith V Monzel, Thomas Budde, Henriette E Meyer Zu Schwabedissen, Matthias Schwebe, Sandra Bien-Möller, Dieter Lütjohann, Heyo K Kroemer, Gabriele Jedlitschky, Markus Grube
The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis...
August 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28801370/impact-of-tlr-2-tlr-4-activation-on-the-expression-of-abca1-and-abcg1-in-raw-cells
#8
Kana Suzuki, Yasushi Kawakami, Kazuyoshi Yamauchi
Toll-like receptors (TLR) activation is thought to modulate the macrophage cholesterol efflux and contribute to the atherosclerosis progression; however, the precise pathophysiological mechanism remains unclear. We investigated the effects of TLR2- and TLR4-activation on the expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 in a mouse macrophage cell line, Raw 264.7. Both TLR2- and TLR4-activation upregulated the expression of ABCA1 mRNA but downregulated that of ABCG1 mRNA. These alterations may be mainly regulated by the following 3 cascades: (1) the TLR/myeloid differentiation primary-response protein 88/Liver X receptor pathway, which upregulated the ABCA1 mRNA; (2) NF-κB pathway, which downregulated the ABCG1 mRNA, and (3) the p38 pathway, which upregulated and stabilized ABCA1 mRNA...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28793908/transcriptomic-analysis-comparing-mouse-strains-with-extreme-total-lung-capacities-identifies-novel-candidate-genes-for-pulmonary-function
#9
Leema George, Ankita Mitra, Tania A Thimraj, Martin Irmler, Sangeetha Vishweswaraiah, Lars Lunding, Dorothea Hühn, Alicia Madurga, Johannes Beckers, Heinz Fehrenbach, Swapna Upadhyay, Holger Schulz, George D Leikauf, Koustav Ganguly
BACKGROUND: Failure to attain peak lung function by early adulthood is a risk factor for chronic lung diseases. Previously, we reported that C3H/HeJ mice have about twice total lung capacity (TLC) compared to JF1/MsJ mice. We identified seven lung function quantitative trait loci (QTL: Lfnq1-Lfnq7) in backcross/intercross mice derived from these inbred strains. We further demonstrated, superoxide dismutase 3, extracellular (Sod3), Kit oncogene (Kit) and secreted phosphoprotein 1 (Spp1) located on these Lfnqs as lung function determinants...
August 9, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28791414/tetramethylpyrazine-suppresses-lipid-accumulation-in-macrophages-via-upregulation-of-the-atp-binding-cassette-transporters-and-downregulation-of-scavenger-receptors
#10
Jie Duan, Dong Xiang, Hongli Luo, Guojun Wang, Yun Ye, Chao Yu, Xiuying Li
Tetramethylpyrazine (TMP), a biologically active ingredient first extracted from the Chinese medicinal plant Ligusticum wallichii Franchat., has athero-protective activity, yet the particular mechanisms have not been completely explored. The present study was designed to investigate the effect of TMP and its possible mechanisms in RAW264.7 macrophages and apolipoprotein E-deficient (ApoE-/-) mice. TMP treatment markedly increased the cholesterol efflux and inhibited oxidized low-density lipoprotein (ox-LDL) uptake, thus, ameliorating lipid accumulation in macrophages...
August 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28775237/c1q-tumor-necrosis-factor-related-protein-3-protects-macrophages-against-lps-induced-lipid-accumulation-inflammation-and-phenotype-transition-via-ppar%C3%AE-and-tlr4-mediated-pathways
#11
Jiale Lin, Qi Liu, Hui Zhang, Xingtao Huang, Ruoxi Zhang, Shuyuan Chen, Xuedong Wang, Bo Yu, Jingbo Hou
Macrophage inflammation and foam cell formation are critical events during the initiation and development of atherosclerosis (AS). C1q/tumor necrosis factor-related protein-3 (CTRP3) is a novel adipokine with anti-inflammatory and cardioprotection properties; however, little is known regarding the influence of CTRP3 on AS. As macrophages play a key role in AS, this study investigated the effects of CTRP3 on macrophage lipid metabolism, inflammatory reactions, and phenotype transition, as well as underlying mechanisms, to reveal the relationship between CTRP3 and AS...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28756295/actin-alpha-cardiac-muscle-1-gene-expression-is-upregulated-in-the-skeletal-muscle-of-men-undergoing-androgen-deprivation-therapy-for-prostate-cancer
#12
Ada S Cheung, Casey de Rooy, Itamar Levinger, Kesha Rana, Michele V Clarke, Jackie M How, Andrew Garnham, Catriona McLean, Jeffrey D Zajac, Rachel A Davey, Mathis Grossmann
Androgen deprivation therapy (ADT) decreases muscle mass and function but no human studies have investigated the underlying genetic or cellular effects. We tested the hypothesis that ADT will lead to changes in skeletal muscle gene expression, which may explain the adverse muscle phenotype seen clinically. We conducted a prospective cohort study of 9 men with localised prostate cancer who underwent a vastus lateralis biopsy before and after 4 weeks of ADT. Next-generation RNA sequencing was performed and genes differentially expressed following ADT underwent gene ontology mining using Ingenuity Pathway Analysis...
July 27, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28739279/eicosapentaenoic-acid-membrane-incorporation-impairs-cholesterol-efflux-from-cholesterol-loaded-human-macrophages-by-reducing-the-cholesteryl-ester-mobilization-from-lipid-droplets
#13
Natalie Fournier, Guillaume Sayet, Benoît Vedie, Maxime Nowak, Fatima Allaoui, Audrey Solgadi, Eric Caudron, Pierre Chaminade, Jean-François Benoist, Jean-Louis Paul
A diet containing a high n-3/n-6 polyunsaturated fatty acids (PUFA) ratio has cardioprotective properties. PUFAs incorporation into membranes influences the function of membrane proteins. We investigated the impact of the membrane incorporation of PUFAs, especially eicosapentaenoic acid (EPA) (C20:5 n-3), on the anti-atherogenic cholesterol efflux pathways. We used cholesteryl esters (CE)-loaded human monocyte-derived macrophages (HMDM) to mimic foam cells exposed to the FAs for a long period of time to ensure their incorporation into cellular membranes...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28736301/foxa-transcriptional-factor-modulates-insect-susceptibility-to-bacillus-thuringiensis-cry1ac-toxin-by-regulating-the-expression-of-toxin-receptor-abcc2-and-abcc3-genes
#14
Jianghuai Li, Yuemin Ma, Wanli Yuan, Yutao Xiao, Chenxi Liu, Jia Wang, Jianxin Peng, Rong Peng, Mario Soberón, Alejandra Bravo, Yongbo Yang, Kaiyu Liu
Cry toxins produced by Bacillus thuringiensis (Bt) are insecticidal proteins widely used in insect control. Recently, it was shown that ATP-binding cassette transporter proteins (ABC) such as ABCC2, ABCC3, ABCG1 and ABCA2 are implicated in the insecticidal action of Cry toxins as putative receptors. However, the transcriptional regulators involved in the expression of ABC transporter genes remain unknown. Sequence analysis of promoter regions of ABCC2 gene from Helicoverpa armigera and ABCC3 gene from Spodoptera litura Sl-HP cultured cells, revealed the potential participation of Forkhead box protein A (FOXA), a transcription factor that regulates the expression of genes through remodeling chromatin...
July 21, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28731176/hypotonic-contrast-media-is-more-toxic-than-isotonic-contrast-media-on-endothelial-cells-in-vivo-and-in-vitro
#15
Lihui Ren, Ping Wang, Zuoyan Wang, Yong Liu, Shuzheng Lv
The aim of the current study was to investigate the cytotoxic effects of hypotonic (iopamidol) and isotonic (iodixanol) contract media (CMs) in vitro and in vivo. A total of 60 Wistar rats were included and were randomly divided into three groups (20 rats per group). Iodixanol (4 g iodine/kg), iopamidol (4 g iodine/kg) or equal volume of normal saline was injected via tail vein. HUVEC and H5V cell viability was determined by Cell Counting Kit‑8 agents. Western blotting was performed to detect ATP‑binding cassette subfamily G member 1 (ABCG1) expression...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710789/atr-101-inhibits-cholesterol-efflux-and-cortisol-secretion-by-atp-binding-cassette-transporters-causing-cytotoxic-cholesterol-accumulation-in-adrenocortical-carcinoma-cells
#16
Veronica Elizabeth Burns, Tom Klaus Kerppola
BACKGROUND AND PURPOSE: To further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR-101 (PD132301-02). EXPERIMENTAL APPROACH: We compared the effects of ATR-101, PD129337, and ABC transporter inhibitors on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC-derived cell lines...
October 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28674080/macrophage-deficiency-of-mir-21-promotes-apoptosis-plaque-necrosis-and-vascular-inflammation-during-atherogenesis
#17
Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Marta Fernández-Fuertes, Cristina Ramírez-Hidalgo, Elisa Araldi, Lidia Daimiel, Rebeca Busto, Carlos Fernández-Hernando, Yajaira Suárez
Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. Here, we define the contribution of miR-21 in hematopoietic cells during atherogenesis. Interestingly, we found that miR-21 is the most abundant miRNA in macrophages and its absence results in accelerated atherosclerosis, plaque necrosis, and vascular inflammation...
September 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28673011/tribbles-homolog-1-enhances-cholesterol-efflux-from-oxidized-low-density-lipoprotein-loaded-thp-1-macrophages
#18
Yanhua Fu, Yang Zhao, Bin Huang
Macrophage foam cell formation plays a pivotal role in the pathogenesis of atherosclerosis. The protein Tribbles homolog 1 (Trib1), a member of the Tribbles protein family, functions as an adaptor or scaffold protein. Recent studies have indicated its implication in lipoprotein metabolism. In the present study, the role of Trib1 in macrophage foam cell formation was investigated. Oil red O staining was used to analyze intracellular lipid deposition, while the effects of Trib1 overexpression on cholesterol efflux were also examined...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28666268/myeloid-specific-genetic-ablation-of-atp-binding-cassette-transporter-abca1-is-protective-against-cancer
#19
Maryam Zamanian-Daryoush, Daniel J Lindner, Joseph A DiDonato, Matthew Wagner, Jennifer Buffa, Patricia Rayman, John S Parks, Marit Westerterp, Alan R Tall, Stanley L Hazen
Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28659806/erythrodiol-an-olive-oil-constituent-increases-the-half-life-of-abca1-and-enhances-cholesterol-efflux-from-thp-1-derived-macrophages
#20
Limei Wang, Sarah Wesemann, Liselotte Krenn, Angela Ladurner, Elke H Heiss, Verena M Dirsch, Atanas G Atanasov
Cholesterol efflux (ChE) from macrophages is an initial step of reverse cholesterol transport (RCT). The ATP-binding cassette transporter A1 (ABCA1) is a key transporter for ChE and its increased expression is regarded to attenuate atherosclerosis. Thus, the identification and characterization of molecules raising ABCA1 and thereby stimulating ChE is of pharmacological relevance. In this study, we tested dietary compounds from olive oil for their capacity of enhancing cellular ABCA1 protein level. We identified erythrodiol (Olean-12-ene-3β,28-diol) as an ABCA1 stabilizer and revealed its positive influence on ChE in THP-1-derived human macrophages...
2017: Frontiers in Pharmacology
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