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Atheroprotective gene expression

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https://www.readbyqxmd.com/read/28432984/cigarette-smoke-extract-counteracts-atheroprotective-effects-of-high-laminar-flow-on-endothelial-function
#1
Sindy Giebe, Natalia Cockcroft, Katherine Hewitt, Melanie Brux, Anja Hofmann, Henning Morawietz, Coy Brunssen
Tobacco smoking and hemodynamic forces are key stimuli in the development of endothelial dysfunction and atherosclerosis. High laminar flow has an atheroprotective effect on the endothelium and leads to a reduced response of endothelial cells to cardiovascular risk factors compared to regions with disturbed or low laminar flow. We hypothesize that the atheroprotective effect of high laminar flow could delay the development of endothelial dysfunction caused by cigarette smoking. Primary human endothelial cells were stimulated with increasing dosages of aqueous cigarette smoke extract (CSEaq)...
April 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28431930/quantitative-proteomics-reveals-key-proteins-regulated-by-eicosapentaenoic-acid-in-endothelial-activation
#2
Lu Zhang, Kunhong Xiao, Xuyang Zhao, Xiaoli Sun, Jianshu Zhang, Xian Wang, Yi Zhu, Xu Zhang
Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid (PUFA), has been shown to decrease the risk of atherosclerosis by attenuating endothelial activation. In this study, we used mass spectrometry-based label-free quantitative proteomics to study the protective mechanisms of EPA and to identify key proteins that regulated by EPA in endothelial activation. Arachidonic acid (AA) was used as a control. HUVECs were pretreated with each of the two PUFAs, and then stimulated with TNFα as a model of endothelial activation...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28292897/inhibition-of-atherogenesis-by-the-cop9-signalosome-subunit-5-in-vivo
#3
Yaw Asare, Miriam Ommer, Florence A Azombo, Setareh Alampour-Rajabi, Marieke Sternkopf, Maryam Sanati, Marion J Gijbels, Corinna Schmitz, Dzmitry Sinitski, Pathricia V Tilstam, Hongqi Lue, André Gessner, Denise Lange, Johannes A Schmid, Christian Weber, Martin Dichgans, Joachim Jankowski, Ruggero Pardi, Menno P J de Winther, Heidi Noels, Jürgen Bernhagen
Constitutive photomorphogenesis 9 (COP9) signalosome 5 (CSN5), an isopeptidase that removes neural precursor cell-expressed, developmentally down-regulated 8 (NEDD8) moieties from cullins (thus termed "deNEDDylase") and a subunit of the cullin-RING E3 ligase-regulating COP9 signalosome complex, attenuates proinflammatory NF-κB signaling. We previously showed that CSN5 is up-regulated in human atherosclerotic arteries. Here, we investigated the role of CSN5 in atherogenesis in vivo by using mice with myeloid-specific Csn5 deletion...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096968/a-novel-atheroprotective-role-of-mf59-like-adjuvant-when-co-administered-with-cetp-vaccine-in-rabbit-model-of-atherosclerosis
#4
Tamara Aghebati, Amir Hooshang Mohammadpour, Mohammad Afshar, Mahmoud Reza Jaafari, Khalil Abnous, Saeed Nazemi, Sobhan Issazadeh, Saeed Hashemzadeh, Mohammad Zare, Ali Badiee
OBJECTIVES: In this study, for the first time, MF59 adjuvant was used to develop a cholesteryl ester transfer protein (CETP) vaccine. The efficacy of the vaccine was compared with the efficacy of CETP vaccine formulated with Alum/CpG, the formulation that its immunogenicity has been already demonstrated in rabbit and mice. MATERIALS AND METHODS: Tetanus toxoid- CETP peptide (TT-CETP) was mixed with Alum/CpG or MF59-like and administered subcutaneously for total five times in rabbit model of atherosclerosis...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28065787/intestinal-farnesoid-x-receptor-controls-transintestinal-cholesterol-excretion-in-mice
#5
Jan Freark de Boer, Marleen Schonewille, Marije Boesjes, Henk Wolters, Vincent W Bloks, Trijnie Bos, Theo H van Dijk, Angelika Jurdzinski, Renze Boverhof, Justina C Wolters, Jan A Kuivenhoven, Jan M van Deursen, Ronald P J Oude Elferink, Antonio Moschetta, Claus Kremoser, Henkjan J Verkade, Folkert Kuipers, Albert K Groen
BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway, however, are poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. METHODS: We performed studies with C57Bl/6J mice, as well as with mice with intestine-specific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-knockout mice...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/27926730/integrin-yap-taz-jnk-cascade-mediates-atheroprotective-effect-of-unidirectional-shear-flow
#6
Li Wang, Jiang-Yun Luo, Bochuan Li, Xiao Yu Tian, Li-Jing Chen, Yuhong Huang, Jian Liu, Dan Deng, Chi Wai Lau, Song Wan, Ding Ai, King-Lun Kingston Mak, Ka Kui Tong, Kin Ming Kwan, Nanping Wang, Jeng-Jiann Chiu, Yi Zhu, Yu Huang
The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli. However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27869741/isoliquiritigenin-attenuates-atherogenesis-in-apolipoprotein-e-deficient-mice
#7
Fen Du, Quzhen Gesang, Jia Cao, Mei Qian, Li Ma, Dongfang Wu, Hong Yu
Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We sought to investigate the effects and mechanism of ISL on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE(-/-)) mice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), while it increased the expression of several lipoprotein-related genes in peritoneal macrophages treated with lipopolysaccharide (LPS)...
November 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27811230/in-vivo-activation-of-leukocyte-gpr120-ffar4-by-pufas-has-minimal-impact-on-atherosclerosis-in-ldl-receptor-knockout-mice
#8
Swapnil V Shewale, Amanda L Brown, Xin Bi, Elena Boudyguina, Janet K Sawyer, Martha A Alexander-Miller, John S Parks
G protein-coupled receptor (GPR)120/FFA receptor (FFAR)4 (GPR120/FFAR4) activation by n-3 PUFAs attenuates inflammation, but its impact on atherosclerosis is unknown. We determined whether in vivo activation of leukocyte GPR120/FFAR4 by n-3 versus n-6 PUFAs is atheroprotective. Leukocyte GPR120/FFAR4 WT or KO mice in the LDL receptor KO background were generated by bone marrow transplantation. Mice were fed one of the four atherogenic diets containing 0.2% cholesterol and 10% calories as palm oil (PO) + 10% calories as: 1) PO, 2) fish oil (FO; 20:5 n-3 and 22:6 n-3 enriched), 3) echium oil (EO; 18:4 n-3 enriched), or 4) borage oil (BO; 18:3 n-6 enriched) for 16 weeks...
January 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/27771368/paraoxonase-and-atherosclerosis-related-cardiovascular-diseases
#9
REVIEW
Dimitry A Chistiakov, Alexandra A Melnichenko, Alexander N Orekhov, Yuri V Bobryshev
In humans, three paraoxonase (PON1, PON2, and PON3) genes are clustered on chromosome 7 at a locus that spans a distance around 170 kb. These genes are highly homologous to each other and have a similar protein structural organization. PON2 is the intracellular enzyme, which is expressed in many tissues and organs, while two other members of PON gene family are produced by liver and associate with high density lipoprotein (HDL). The lactonase activity is the ancestral. Besides lactones and organic phosphates, PONs can hydrolyze and therefore detoxify oxidized low density lipoprotein and homocysteine thiolactone, i...
January 2017: Biochimie
https://www.readbyqxmd.com/read/27680891/macrophages-of-genetically-characterized-familial-hypercholesterolaemia-patients-show-up-regulation-of-ldl-receptor-related-proteins
#10
Rafael Escate, Teresa Padro, Maria Borrell-Pages, Rosa Suades, Rosa Aledo, Pedro Mata, Lina Badimon
Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL...
March 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27573737/macrophage-molecular-signaling-and-inflammatory-responses-during-ingestion-of-atherogenic-lipoproteins-are-modulated-by-complement-protein-c1q
#11
Minh-Minh Ho, Ayla Manughian-Peter, Weston R Spivia, Adam Taylor, Deborah A Fraser
BACKGROUND AND AIMS: This study investigated the effect of innate immune protein C1q on macrophage programmed responses during the ingestion of atherogenic lipoproteins. C1q plays a dual role in atherosclerosis where activation of complement by C1q is known to drive inflammation and promote disease progression. However, C1q is atheroprotective in early disease using mouse models. Our previous studies have highlighted a non-complement associated role for C1q in polarizing macrophages towards an M2-like anti-inflammatory phenotype during ingestion of targets such as atherogenic lipoproteins...
October 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27445103/nox4-derived-reactive-oxygen-species-limit-fibrosis-and-inhibit-proliferation-of-vascular-smooth-muscle-cells-in-diabetic-atherosclerosis
#12
Elyse Di Marco, Stephen P Gray, Kit Kennedy, Cedric Szyndralewiez, Alicia N Lyle, Bernard Lassègue, Kathy K Griendling, Mark E Cooper, Harald H H W Schmidt, Karin A M Jandeleit-Dahm
Smooth muscle cell (SMC) proliferation and fibrosis contribute to the development of advanced atherosclerotic lesions. Oxidative stress caused by increased production or unphysiological location of reactive oxygen species (ROS) is a known major pathomechanism. However, in atherosclerosis, in particular under hyperglycaemic/diabetic conditions, the hydrogen peroxide-producing NADPH oxidase type 4 (NOX4) is protective. Here we aim to elucidate the mechanisms underlying this paradoxical atheroprotection of vascular smooth muscle NOX4 under conditions of normo- and hyperglycaemia both in vivo and ex vivo...
August 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27404994/development-of-a-synthetic-gene-network-to-modulate-gene-expression-by-mechanical-forces
#13
Zoltán Kis, Tania Rodin, Asma Zafar, Zhangxing Lai, Grace Freke, Oliver Fleck, Armando Del Rio Hernandez, Leila Towhidi, Ryan M Pedrigi, Takayuki Homma, Rob Krams
The majority of (mammalian) cells in our body are sensitive to mechanical forces, but little work has been done to develop assays to monitor mechanosensor activity. Furthermore, it is currently impossible to use mechanosensor activity to drive gene expression. To address these needs, we developed the first mammalian mechanosensitive synthetic gene network to monitor endothelial cell shear stress levels and directly modulate expression of an atheroprotective transcription factor by shear stress. The technique is highly modular, easily scalable and allows graded control of gene expression by mechanical stimuli in hard-to-transfect mammalian cells...
July 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27315776/proatherosclerotic-effect-of-the-%C3%AE-1-subunit-of-soluble-guanylyl-cyclase-by-promoting-smooth-muscle-phenotypic-switching
#14
Maria Segura-Puimedon, Evanthia Mergia, Jaafar Al-Hasani, Redouane Aherrahrou, Stephanie Stoelting, Felix Kremer, Jennifer Freyer, Doris Koesling, Jeanette Erdmann, Heribert Schunkert, Cor de Wit, Zouhair Aherrahrou
Soluble guanylate cyclase (sGC), a key enzyme of the nitric oxide signaling pathway, is formed as a heterodimer by various isoforms of its α and β subunit. GUCY1A3, encoding the α1 subunit, was identified as a risk gene for coronary artery disease and myocardial infarction, but its specific contribution to atherosclerosis remains unclear. This study sought to decipher the role of Gucy1a3 in atherosclerosis in mice. At age 32 weeks and after 20 weeks of standard or high-fat diet, Gucy1a3(-/-)/Ldlr(-/-) mice exhibited a significant reduction of the atherosclerotic plaque size at the aortic root and the aorta for high-fat diet animals as compared with Ldlr(-/-) control mice...
August 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27295628/atheroprotective-laminar-flow-inhibits-hippo-pathway-effector-yap-in-endothelial-cells
#15
Suowen Xu, Marina Koroleva, Meimei Yin, Zheng Gen Jin
Atherosclerosis is a mechanobiology-related disease that preferentially develops in the aortic arch and arterial branches, which are exposed to disturbed/turbulent blood flow but less in thoracic aorta where the flow pattern is steady laminar flow (LF). Increasing evidence supports that steady LF with high shear stress is protective against atherosclerosis. However, the molecular mechanisms of LF-mediated atheroprotection remain incompletely understood. Hippo/YAP (yes-associated protein) pathway senses and effects mechanical cues and has been reported to be a master regulator of cell proliferation, differentiation, and tissue homeostasis...
October 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27199450/deficiency-of-atp-binding-cassette-transporters-a1-and-g1-in-endothelial-cells-accelerates-atherosclerosis-in-mice
#16
Marit Westerterp, Kyoichiro Tsuchiya, Ian W Tattersall, Panagiotis Fotakis, Andrea E Bochem, Matthew M Molusky, Vusisizwe Ntonga, Sandra Abramowicz, John S Parks, Carrie L Welch, Jan Kitajewski, Domenico Accili, Alan R Tall
OBJECTIVE: Plasma high-density lipoproteins have several putative antiatherogenic effects, including preservation of endothelial functions. This is thought to be mediated, in part, by the ability of high-density lipoproteins to promote cholesterol efflux from endothelial cells (ECs). The ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) interact with high-density lipoproteins to promote cholesterol efflux from ECs. To determine the impact of endothelial cholesterol efflux pathways on atherogenesis, we prepared mice with endothelium-specific knockout of Abca1 and Abcg1...
July 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26914137/heat-killed-staphylococcus-aureus-reduces-atherosclerosis-by-inducing-anti-inflammatory-macrophages
#17
V Frodermann, J van Duijn, G H M van Puijvelde, P J van Santbrink, H M Lagraauw, M R de Vries, P H A Quax, I Bot, A C Foks, S C A de Jager, J Kuiper
BACKGROUND: Staphylococcus aureus cell wall components can induce IL-10 responses by immune cells, which may be atheroprotective. Therefore, in this study, we investigated whether heat-killed S. aureus (HK-SA) could inhibit the development of atherosclerosis. METHODS: Atherosclerosis-susceptible LDL receptor-deficient mice were administered intraperitoneal HK-SA twice weekly and fed a Western-type diet for 6 weeks. RESULTS: HK-SA administration resulted in a 1...
June 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/26869447/mirnas-and-high-density-lipoprotein-metabolism
#18
Ángel Baldán, Thomas Q de Aguiar Vallim
Altered lipoprotein metabolism plays a key role during atherogenesis. For over 50years, epidemiological data have fueled the proposal that HDL-cholesterol (HDL-c) in circulation is inversely correlated to cardiovascular risk. However, the atheroprotective role of HDL is currently the focus of much debate and remains an active field of research. The emerging picture from research in the past decade suggests that HDL function, rather than HDL-c content, is important in disease. Recent developments demonstrate that miRNAs play an important role in fine-tuning the expression of key genes involved in HDL biogenesis, lipidation, and clearance, as well as in determining the amounts of HDL-c in circulation...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26842974/lipid-lowering-hepatoprotective-and-atheroprotective-effects-of-the-mixture-hong-qu-and-gypenosides-in-hyperlipidemia-with-nafld-rats
#19
San-Hu Gou, Hai-Feng Huang, Xin-Yue Chen, Jie Liu, Miao He, Yin-Yun Ma, Xiao-Ning Zhao, Yun Zhang, Jing-Man Ni
BACKGROUND: Hyperlipidemia and its complications are among the most harmful of diseases with a worldwide impact, which creates an urgent imperative to find safe and effective drugs for treatment. HG is mainly composed of two kinds of traditional Chinese medicines (TCM), Hong-Qu and gypenosides. Previously, the ingredients of the mixture mainly composed by Hong-Qu and gypenosides (HG) were widely used for purposes of lipid-lowering, antiatherosclerosis effects, and maintaining cardiovascular health in China...
March 2016: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/26821299/genetic-loci-on-chromosome-5-are-associated-with-circulating-levels-of-interleukin-5-and-eosinophil-count-in-a-european-population-with-high-risk-for-cardiovascular-disease
#20
Olga McLeod, Angela Silveira, Elsa Valdes-Marquez, Harry Björkbacka, Peter Almgren, Karl Gertow, Jesper R Gådin, Alexandra Bäcklund, Bengt Sennblad, Damiano Baldassarre, Fabrizio Veglia, Steve E Humphries, Elena Tremoli, Ulf de Faire, Jan Nilsson, Olle Melander, Jemma C Hopewell, Robert Clarke, Hanna M Björck, Anders Hamsten, John Öhrvik, Rona J Strawbridge
IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits...
May 2016: Cytokine
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