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Atheroprotective gene expression

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https://www.readbyqxmd.com/read/28500253/linc00341-exerts-an-anti-inflammatory-effect-on-endothelial-cells-by-repressing-vcam1
#1
Tse-Shun Huang, Kuei-Chun Wang, Sara Quon, Phu Nguyen, Ting-Yu Chang, Zhen Chen, Yi-Shuan Li, Shankar Subramaniam, John Y-J Shyy, Shu Chien
The long non-coding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells...
May 12, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28475147/folic-acid-supplementation-delays-atherosclerotic-lesion-development-by-modulating-mcp1-and-vegf-dna-methylation-levels-in-vivo-and-in-vitro
#2
Shanshan Cui, Wen Li, Xin Lv, Pengyan Wang, Yuxia Gao, Guowei Huang
The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells...
May 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28473437/endothelial-myocyte-enhancer-factor-2c-inhibits-migration-of-smooth-muscle-cells-through-fenestrations-in-the-internal-elastic-lamina
#3
Yao Wei Lu, Anthony M Lowery, Li-Yan Sun, Harold A Singer, Guohao Dai, Alejandro P Adam, Peter A Vincent, John J Schwarz
OBJECTIVE: Laminar flow activates myocyte enhancer factor 2 (MEF2) transcription factors in vitro to induce expression of atheroprotective genes in the endothelium. Here we sought to establish the role of Mef2c in the vascular endothelium in vivo. APPROACH AND RESULTS: To study endothelial Mef2c, we generated endothelial-specific deletion of Mef2c using Tie2-Cre or Cdh5-Cre-ER(T2) and examined aortas and carotid arteries by en face immunofluorescence. We observed enhanced actin stress fiber formation in the Mef2c-deleted thoracic aortic endothelium (laminar flow region), similar to those observed in normal aortic inner curvature (disturbed flow region)...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28450349/vascular-cxcr4-limits-atherosclerosis-by-maintaining-arterial-integrity-evidence-from-mouse-and-human-studies
#4
Yvonne Döring, Heidi Noels, Emiel P C van der Vorst, Carlos Neideck, Virginia Egea, Maik Drechsler, Manuela Mandl, Lukas B Pawig, Yvonne Jansen, Katrin Schröder, Kiril Bidzhekov, Remco T A Megens, Wendy Theelen, Barbara M Klinkhammer, Peter Boor, Leon J Schurgers, Rick H van Gorp, Christian Ries, Pascal J H Kusters, Allard C van der Wal, Tilman M Hackeng, Gabor Gäbel, Ralf P Brandes, Oliver Soehnlein, Esther Lutgens, Dietmar Vestweber, Daniel Teupser, Lesca M Holdt, Daniel J Rader, Danish Saleheen, Christian Weber
Background -The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of CXCL12/CXCR4 has only been implied through pharmacological intervention, particularly as the somatic deletion of the CXCR4 gene in mice is embryonically lethal. Moreover, cell-specific effects of CXCR4 in the arterial wall and underlying mechanisms remain elusive, prompting us to investigate the relevance of CXCR4 in vascular cell types for atheroprotection...
April 27, 2017: Circulation
https://www.readbyqxmd.com/read/28432984/cigarette-smoke-extract-counteracts-atheroprotective-effects-of-high-laminar-flow-on-endothelial-function
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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