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Atheroprotective gene expression

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https://www.readbyqxmd.com/read/28811527/atherosusceptible-shear-stress-activates-endoplasmic-reticulum-stress-to-promote-endothelial-inflammation
#1
Keith A Bailey, Fawaz G Haj, Scott I Simon, Anthony G Passerini
Atherosclerosis impacts arteries where disturbed blood flow renders the endothelium susceptible to inflammation. Cytokine activation of endothelial cells (EC) upregulates VCAM-1 receptors that target monocyte recruitment to atherosusceptible regions. Endoplasmic reticulum (ER) stress elicits EC dysregulation in metabolic syndrome. We hypothesized that ER plays a central role in mechanosensing of atherosusceptible shear stress (SS) by signaling enhanced inflammation. Aortic EC were stimulated with low-dose TNFα (0...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794002/klf4-regulation-of-ch25h-and-lxr-mitigates-atherosclerosis-susceptibility
#2
Zhao Li, Marcy Martin, Jin Zhang, Hsi-Yuan Huang, Liang Bai, Jiao Zhang, Jian Kang, Ming He, Jie Li, Mano R Maurya, Shakti Gupta, Guangjin Zhou, Panjamaporn Sangwung, Yong-Jiang Xu, Ting Lei, Hsien-Da Huang, Mohit Jain, Mukesh K Jain, Shankar Subramaniam, John Y-J Shyy
Background -Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall [e.g., endothelial cells (ECs)] as well as circulating and resident immunogenic cells (e.g., monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of sterol regulatory element binding protein 2 (SREBP2), 25-hydroxycholesterol (25-HC) and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages...
August 9, 2017: Circulation
https://www.readbyqxmd.com/read/28771708/metabolic-profiling-of-murine-plasma-reveals-eicosapentaenoic-acid-metabolites-protecting-against-endothelial-activation-and-atherosclerosis
#3
Yajin Liu, Xuan Fang, Xu Zhang, Jing Huang, Jinlong He, Liyuan Peng, Chenji Ye, Yingmei Wang, Fengxia Xue, Ding Ai, Dan Li, Yi Zhu
BACKGROUND AND PURPOSE: Atherosclerosis results from a maladaptive inflammatory response initiated by the intramural retention of LDL in susceptible areas of the arterial vasculature. ω-3 polyunsaturated fatty acids (ω-3) have protective effects in atherosclerosis; however, the molecular mechanism is still largely unknown. The present study used a metabolomic approach to reveal the atheroprotective metabolites of ω-3 and investigate the underlying mechanisms. EXPERIMENTAL APPROACH: We evaluated the development of atherosclerosis in LDL-receptor-deficient mice (LDLR(-/-) ) fed a Western-type diet (WTD) plus ω-3 and also LDLR(-/-) and fat-1 transgenic (LDLR(-/-) -fat-1(tg) ) mice fed a WTD...
August 3, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28740544/interleukin-32%C3%AE-inhibits-endothelial-inflammation-vascular-smooth-muscle-cell-activation-and-atherosclerosis-by-upregulating-timp3-and-reck-through-suppressing-microrna-205-biogenesis
#4
Dong Ju Son, Yu Yeon Jung, Young Sik Seo, Heonyong Park, Dong Hun Lee, Sanghyeon Kim, Yoon-Seok Roh, Sang Bae Han, Do Young Yoon, Jin Tae Hong
Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and regulates vascular endothelial cell behavior. Although some IL-32 isoforms have been reported to contribute to vascular inflammation and atherosclerosis, the functional role of IL-32α in vascular inflammation and atherogenesis has not been studied. Methods: IL-32α function was assessed in cells with transient IL-32α overexpression or treated with recombinant human IL-32α by western blotting and mRNA expression analysis. Vascular smooth muscle cell (VSMC) proliferation and migration was examined by BrdU incorporation and wound healing assays, respectively...
2017: Theranostics
https://www.readbyqxmd.com/read/28560417/atheroprotective-effects-of-statins-in-patients-with-unstable-angina-by-regulating-the-blood-borne-microrna-network
#5
Sufang Li, Chengfu Cao, Hong Chen, Junxian Song, Chongyou Lee, Jing Zhang, Feng Zhang, Qiang Geng, Zheng Li, Jingjin Li
Experimental studies have demonstrated several effects of statins in acute coronary syndrome (ACS) that may extend their clinical benefit beyond the lipid profile modification itself. However, the precise underlying mechanism remains to be elucidated. microRNAs (miRNAs) serve significant roles in the pathophysiology of atherosclerotic plaque progression. The present study investigated the protective role of statins in patients with unstable angina (UA) by regulating the circulating miRNA network. miRNA array results demonstrated that there were 21 differentially expressed miRNAs in non‑statin‑treated patients with UA (n=8) compared with non‑coronary artery disease controls (n=8), and 33 differentially expressed miRNAs in statin‑treated patients with UA (n=8) compared with non‑statin patients...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28500253/linc00341-exerts-an-anti-inflammatory-effect-on-endothelial-cells-by-repressing-vcam1
#6
Tse-Shun Huang, Kuei-Chun Wang, Sara Quon, Phu Nguyen, Ting-Yu Chang, Zhen Chen, Yi-Shuan Li, Shankar Subramaniam, John Shyy, Shu Chien
The long noncoding 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...
July 1, 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
#7
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
#8
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)...
July 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
#9
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
#10
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)...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28431930/quantitative-proteomics-reveals-key-proteins-regulated-by-eicosapentaenoic-acid-in-endothelial-activation
#11
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...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28292897/inhibition-of-atherogenesis-by-the-cop9-signalosome-subunit-5-in-vivo
#12
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
#13
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
#14
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...
April 2017: Gastroenterology
https://www.readbyqxmd.com/read/27926730/integrin-yap-taz-jnk-cascade-mediates-atheroprotective-effect-of-unidirectional-shear-flow
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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