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Atheroprotective gene expression

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https://www.readbyqxmd.com/read/27869741/isoliquiritigenin-attenuates-atherogenesis-in-apolipoprotein-e-deficient-mice
#1
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-polyunsaturated-fatty-acids-has-minimal-impact-on-atherosclerosis-in-ldl-receptor-knockout-mice
#2
Swapnil V Shewale, Amanda L Brown, Xin Bi, Elena Boudyguina, Janet K Sawyer, Martha A Alexander-Miller, John S Parks
G protein-coupled receptor 120 (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 vs. n-6 PUFA 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...
November 3, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27771368/paraoxonase-and-atherosclerosis-related-cardiovascular-diseases
#3
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...
October 19, 2016: Biochimie
https://www.readbyqxmd.com/read/27680891/macrophages-of-genetically-characterized-familial-hypercholesterolaemia-patients-show-up-regulation-of-ldl-receptor-related-proteins
#4
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...
September 29, 2016: 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
#5
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
#6
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
#7
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...
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/26721343/imatinib-reduces-cholesterol-uptake-and-matrix-metalloproteinase-activity-in-human-thp-1-macrophages
#15
Jelena Gacic, Emina Vorkapic, Renate Slind Olsen, Daniel Söderberg, Therese Gustafsson, Robert Geffers, Karin Skoglund, Andreas Matussek, Dick Wågsäter
BACKGROUND: Imatinib mesylate (Glivec®, formerly STI-571) is a selective tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. However, there are reports suggesting that imatinib could be atheroprotective by lowering plasma low-density lipoprotein (LDL). AIM: To investigate the potential inhibitory effect of imatinib on cholesterol uptake in human macrophages as well as its effect on matrix metalloproteinase (MMP) activity...
February 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/26715682/reactive-oxygen-species-can-provide-atheroprotection-via-nox4-dependent-inhibition-of-inflammation-and-vascular-remodeling
#16
Stephen P Gray, Elyse Di Marco, Kit Kennedy, Phyllis Chew, Jun Okabe, Assam El-Osta, Anna C Calkin, Erik A L Biessen, Rhian M Touyz, Mark E Cooper, Harald H H W Schmidt, Karin A M Jandeleit-Dahm
OBJECTIVE: Oxidative stress is considered a hallmark of atherosclerosis. In particular, the superoxide-generating type 1 NADPH oxidase (NOX1) has been shown to be induced and play a pivotal role in early phases of mouse models of atherosclerosis and in the context of diabetes mellitus. Here, we investigated the role of the most abundant type 4 isoform (NOX4) in human and mouse advanced atherosclerosis. APPROACH AND RESULTS: Plaques of patients with cardiovascular events or established diabetes mellitus showed a surprising reduction in expression of the most abundant but hydrogen peroxide (H2O2)-generating type 4 isoform (Nox4), whereas Nox1 mRNA was elevated, when compared with respective controls...
February 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26681753/carboxyl-terminal-cleavage-of-apolipoprotein-a-i-by-human-mast-cell-chymase-impairs-its-anti-inflammatory-properties
#17
Su Duy Nguyen, Katariina Maaninka, Jani Lappalainen, Katariina Nurmi, Jari Metso, Katariina Öörni, Mohamad Navab, Alan M Fogelman, Matti Jauhiainen, Miriam Lee-Rueckert, Petri T Kovanen
OBJECTIVE: Apolipoprotein A-I (apoA-I) has been shown to possess several atheroprotective functions, including inhibition of inflammation. Protease-secreting activated mast cells reside in human atherosclerotic lesions. Here we investigated the effects of the neutral proteases released by activated mast cells on the anti-inflammatory properties of apoA-I. APPROACH AND RESULTS: Activation of human mast cells triggered the release of granule-associated proteases chymase, tryptase, cathepsin G, carboxypeptidase A, and granzyme B...
February 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26603156/s1p2-g12-13-signaling-negatively-regulates-macrophage-activation-and-indirectly-shapes-the-atheroprotective-b1-cell-population
#18
Myriam Grimm, Denise Tischner, Kerstin Troidl, Julián Albarrán Juárez, Kishor K Sivaraj, Nerea Ferreirós Bouzas, Gerd Geisslinger, Christoph J Binder, Nina Wettschureck
OBJECTIVES: Monocyte/macrophage recruitment and activation at vascular predilection sites plays a central role in the pathogenesis of atherosclerosis. Heterotrimeric G proteins of the G12/13 family have been implicated in the control of migration and inflammatory gene expression, but their function in myeloid cells, especially during atherogenesis, is unknown. APPROACH AND RESULTS: Mice with myeloid-specific deficiency for G12/13 show reduced atherosclerosis with a clear shift to anti-inflammatory gene expression in aortal macrophages...
January 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/26566121/blue-green-algae-inhibit-the-development-of-atherosclerotic-lesions-in-apolipoprotein-e-knockout-mice
#19
Chai Siah Ku, Bohkyung Kim, Tho X Pham, Yue Yang, Casey J Wegner, Young-Ki Park, Marcy Balunas, Ji-Young Lee
Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE(-/-)) mice, a well-established mouse model of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks...
December 2015: Journal of Medicinal Food
https://www.readbyqxmd.com/read/26521149/leptin-dose-dependently-decreases-atherosclerosis-by-attenuation-of-hypercholesterolemia-and-induction-of-adiponectin
#20
Annett Hoffmann, Thomas Ebert, Nora Klöting, Janine Dokas, Franziska Jeromin, Beate Jessnitzer, Ralph Burkhardt, Mathias Fasshauer, Susan Kralisch
OBJECTIVES: Conflicting evidence concerning leptin in atherosclerosis has been published. Furthermore, dose-dependent effects of leptin on atherogenesis have not been studied. METHODS: Leptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR(-/-);ob/ob) mice were treated with saline, 0.1, 0.5, or 3.0mg/kg body weight (BW)/d recombinant leptin over 12weeks starting at 8weeks of age. Aortic root and brachiocephalic artery (BCA) atherosclerotic lesions were analyzed by oil red O staining...
January 2016: Biochimica et Biophysica Acta
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