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Antiinflammatory cytokines and atherosclerosis

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
Adriélly F Santanna, Placielle F Filete, Ewelyne M Lima, Marcella L Porto, Silvana S Meyrelles, Elisardo C Vasquez, Denise C Endringer, Dominik Lenz, Dulcineia S P Abdalla, Thiago M C Pereira, Tadeu U Andrade
OBJECTIVES: Kefir is obtained by the action of acidic bacteria and yeasts that exist in symbiotic association in kefir grains. Recently, this fermented milk drink has been recommended for the treatment of several clinical conditions, such as inflammatory, gastrointestinal, or cardiovascular-related diseases, or a combination of these diseases. However, its effects on atherosclerosis are not yet clear. The aim of this study was to prove that chronic treatment with a soluble, nonbacterial fraction of kefir could reduce the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice...
March 2017: Nutrition
Zoltán Szekanecz, György Kerekes, Edit Végh, Zsófia Kardos, Zsuzsa Baráth, László Tamási, Yehuda Shoenfeld
Autoimmune-inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) have been associated with autoimmune atherosclerosis leading to increased cardiovascular risk. Traditional risk factors, genetics, as well as the role of systemic inflammation including inflammatory cells, cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. Cardiovascular risk may be determined by the use of currently available tools...
July 2016: Autoimmunity Reviews
Lai Yen Fong, Chin Theng Ng, Zainul Amiruddin Zakaria, Mohamad Taufik Hidayat Baharuldin, Abdul Kadir Arifah, Muhammad Nazrul Hakim, Ahmad Zuraini
The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC)...
October 2015: Phytotherapy Research: PTR
Glen C Jickling, DaZhi Liu, Bradley P Ander, Boryana Stamova, Xinhua Zhan, Frank R Sharp
Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood-brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis...
June 2015: Journal of Cerebral Blood Flow and Metabolism
Bin Deng, Fang Fang, Tianlu Yang, Zaixin Yu, Bin Zhang, Xiumei Xie
AIM: Ghrelin, a gastric peptide, is involved in several metabolic and cardiovascular processes. Emerging evidence indicates the potential involvement of ghrelin in low-grade inflammatory diseases such as atherosclerosis and hypertension. Cytokine-induced inflammation is critical in these pathological states. The growth hormone secretagogue receptor (GHSR) has been identified in blood vessels, so we predict that ghrelin might inhibit proinflammatory responses in human umbilical vein endothelial cells (HUVECs)...
2015: International Journal of Clinical and Experimental Medicine
Mario Adán Moreno-Eutimio, Gustavo Acosta-Altamirano
Sedentary lifestyle leads to the accumulation of visceral fat. This is accompanied by the infiltration of immune cells with pro-inflammatory characteristics in adipose tissue, causing an increased release of cytokines and generating a low-grade inflammatory state. It has been associated with the development of insulin resistance, atherosclerosis, neurodegeneration, and development of tumors. Exercise can be used as a treatment to improve symptoms of many of these conditions because it promotes an anti-inflammatory effect...
May 2014: Cirugia y Cirujanos
Carolyn L Geczy, Yuen Ming Chung, Yuka Hiroshima
S100A8, S100A9 and S100A12 are considered proinflammatory mediators of atherosclerosis. Known as calgranulins, they are major components of neutrophils and are upregulated in macrophages and foam cells. They influence leukocyte recruitment, and may propagate inflammation by binding TLR4 and/or receptor for advanced glycation endproducts (RAGE). However, the receptors for calgranulins remain an enigma; we have no evidence for TLR4 or RAGE activation by S100A8 or S100A12. Moreover, gene regulation studies suggest antiinflammatory functions for S100A8 and emerging reports indicate pleiotropic roles...
2014: Circulation Journal: Official Journal of the Japanese Circulation Society
Huaiping Yuan, Sami Zelkha, Sami Zelka, Marina Burkatovskaya, Rohit Gupte, Susan E Leeman, Salomon Amar
The purpose of this study was to elucidate the role of nucleotide binding oligomerization domain-containing protein 2 (NOD2) signaling in atherosclerosis and periodontal bone loss using an Apolipoprotein E(-/-) (ApoE(-/-)) mouse model based on the proposed role of NOD2 in inflammation. NOD2(-/-)ApoE(-/-) and ApoE(-/-) mice fed a standard chow diet were given an oral gavage of Porphyromonas gingivalis for 15 wk. NOD2(-/-)ApoE(-/-) mice exhibited significant increases in inflammatory cytokines, alveolar bone loss, cholesterol, and atherosclerotic lesions in the aorta and the heart compared with ApoE(-/-) mice...
December 24, 2013: Proceedings of the National Academy of Sciences of the United States of America
Lina Ma, Xueqing Liu, Yanyang Zhao, Beidong Chen, Xingguang Li, Ruomei Qi
Oxidized low-density lipoprotein (ox-LDL) is an important risk factor in the development of atherosclerosis. LOX-1, a lectin-like receptor for ox-LDL, is present primarily on endothelial cells and upregulated by ox-LDL, tumor necrosis factor a, shear stress, and cytokines in atherosclerosis. Recent studies demonstrated that ginkgolide B, a platelet-activating factor receptor antagonist, has antiinflammatory and antioxidant effects on endothelial and nerve cells. The present study investigated the effects of ginkgolide B on LOX-1 expression and the possible mechanism of action...
2013: PloS One
Aynur Küçükçongar, Idil Yenicesu, Leyla Tümer, Ciğdem Seher Kasapkara, Fatih Süheyl Ezgü, Ozge Paşaoğlu, Canan Demirtaş, Bülent Celik, Günter Dilsiz, Alev Hasanoğlu
Familial hypercholesterolemia is a genetic disorder that leads to severe atherosclerosis related cardiovascular complications in young adults. Extracorporeal elimination is a method of LDL-lowering procedures effective in patients with homozygous or severe heterozygous FH utilized in cases. The recruitment of leucocytes into the arterial intima is dependent on a cascade of events mediated through a diverse family of adhesion molecules. Several pro-inflammatory adhesion molecules are cleared by various lipid apheresis methods...
June 2013: Transfusion and Apheresis Science
Omar M Khan, Murali K Akula, Kristina Skålen, Christin Karlsson, Marcus Ståhlman, Stephen G Young, Jan Borén, Martin O Bergo
BACKGROUND: Statins have antiinflammatory and antiatherogenic effects that have been attributed to inhibition of RHO protein geranylgeranylation in inflammatory cells. The activity of protein geranylgeranyltransferase type I (GGTase-I) is widely believed to promote membrane association and activation of RHO family proteins. However, we recently showed that knockout of GGTase-I in macrophages activates RHO proteins and proinflammatory signaling pathways, leading to increased cytokine production and rheumatoid arthritis...
February 19, 2013: Circulation
Xiu-Fen Ming, Angana G Rajapakse, Gautham Yepuri, Yuyan Xiong, João M Carvas, Jean Ruffieux, Isabelle Scerri, Zongsong Wu, Katja Popp, Jianhui Li, Claudio Sartori, Urs Scherrer, Brenda R Kwak, Jean-Pierre Montani, Zhihong Yang
BACKGROUND: Macrophage-mediated chronic inflammation is mechanistically linked to insulin resistance and atherosclerosis. Although arginase I is considered antiinflammatory, the role of arginase II (Arg-II) in macrophage function remains elusive. This study characterizes the role of Arg-II in macrophage inflammatory responses and its impact on obesity-linked type II diabetes mellitus and atherosclerosis. METHODS AND RESULTS: In human monocytes, silencing Arg-II decreases the monocytes' adhesion to endothelial cells and their production of proinflammatory mediators stimulated by oxidized low-density lipoprotein or lipopolysaccharides, as evaluated by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay...
August 2012: Journal of the American Heart Association
Apostolos Polykratis, Geert van Loo, Sofia Xanthoulea, Martin Hellmich, Manolis Pasparakis
BACKGROUND: Previous studies implicated Toll-like receptor signaling as a critical pathogenic pathway in atherosclerosis, but the cell-specific mechanisms by which Toll-like receptors act to control atherosclerotic plaque development remain poorly understood. METHODS AND RESULTS: To study the cell-specific role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in atherosclerosis, we generated ApoE(-/-) mice with endothelial cell- or myeloid cell-specific TRAF6 deficiency using Cre/LoxP-mediated gene targeting...
October 2, 2012: Circulation
Antoine Makdissi, Husam Ghanim, Mehul Vora, Kelly Green, Sanaa Abuaysheh, Ajay Chaudhuri, Sandeep Dhindsa, Paresh Dandona
CONTEXT: Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-IV (DPP-IV), which degrades the incretins, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, and thus, sitagliptin increases their bioavailability. The stimulation of insulin and the suppression of glucagon secretion that follow exert a glucose lowering effect and hence its use as an antidiabetic drug. Because DPP-IV is expressed as CD26 on cell membranes and because CD26 mediates proinflammatory signals, we hypothesized that sitagliptin may exert an antiinflammatory effect...
September 2012: Journal of Clinical Endocrinology and Metabolism
Claudia Stefanutti, Serafina Di Giacomo, Claudia Morozzi
LDL apheresis (LDLa) is an invasive therapeutic tool to control qualitative and quantitative disorders of lipid metabolism. It is aimed at achieving a metabolic balance in association with lipid-lowering drugs in patients with severe, genetically determined or acquired dyslipidemia who do not reach clinically adequate LDL-cholesterol (LDL-C) levels (<70 mg/dL) despite appropriate lipid-lowering drug treatment. A poorly known dyslipidemia is constituted by elevation of lipoprotein (a) [Lp(a)], which appears to be genetically determined and not influenced by diet or lipid-lowering medication...
January 2012: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Xiao Meng, Kai Zhang, Jingjing Li, Mei Dong, Jianmin Yang, Guipeng An, Weidong Qin, Fei Gao, Cheng Zhang, Yun Zhang
CD4⁺CD25⁺ regulatory T cells (Tregs) mediate immune suppression and prevent autoimmune disorders. Recently, Tregs were found to present in atherosclerotic lesions and play an important role in the progression of atherosclerosis. Statins have immunomodulatory properties, and the effect of statins on atherosclerosis depends in part on their immunomodulatory mechanisms. We sought to determine whether statins exhibit an effect on Tregs in atherosclerotic plaques and in peripheral circulation of patients with acute coronary syndrome (ACS)...
2012: Molecular Medicine
Chary Lopez-Pedrera, Patricia Ruiz-Limon, Araceli Valverde-Estepa, Nuria Barbarroja, Antonio Rodriguez-Ariza
Statins have been successfully used in patients with hypercholesterolemia and cardiovascular diseases, but there is increasing evidence that they exert effects by much exceeding the lowering of cholesterol levels. Statins have antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and antithrombotic effects. These "pleiotropic" effects stem from their inhibition of prenylation of the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts)...
June 2012: Current Drug Targets
Daniel J Rader
Inflammation is a critical component of atherosclerosis. IL-1 is a classic proinflammatory cytokine that has been linked to atherosclerosis. A clinical trial has been launched in which an antibody specific for IL-1β is being studied for its effects on cardiovascular events in patients with atherosclerosis. In this issue of the JCI, Alexander et al. report that mice lacking the receptor for IL-1 unexpectedly have features of advanced atherosclerosis that suggest the atherosclerotic plaques may be less stable...
January 2012: Journal of Clinical Investigation
Kyoichiro Tsuchiya, Alexander S Banks, Chien-Ping Liang, Ira Tabas, Alan R Tall, Domenico Accili
OBJECTIVE: Insulin resistance renders macrophages more prone to cholesterol-induced apoptosis by promoting nuclear localization of transcription factor forkhead box transcription factor (Fox) O1. However, FoxO1 also decreases macrophage inflammation, raising the question of how the balance between proapoptotic and antiinflammatory effects is determined. We sought to identify the mechanism whereby FoxO1 dampens inflammation without promoting apoptosis. We hypothesized that nutrient-dependent FoxO1 acetylation plays a role in this process...
December 2011: Arteriosclerosis, Thrombosis, and Vascular Biology
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