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Gene expression in lymphocytes and atherosclerosis

Zhangyong Xia, Mingliang Gu, Xiaodong Jia, Xiaoting Wang, Chunxia Wu, Jiangwen Guo, Liyong Zhang, Yifeng Du, Jiyue Wang
Atherosclerosis (AS) is a multifactorial disease. Exploration of DNA methylation in regulating gene transcription in a cell type- and stage-specific manner will shed light on understanding the biological processes associated with plaque stability. We identified 174 up-regulated genes with hypo-methylation in the promoter, and 86 down-regulated genes with hyper-methylation in the promoter, in AS vs. healthy controls. Among them, high expression of signaling lymphocytic activation molecule 7 (SLAM7) was examined in carotid plaque vs...
June 13, 2018: Aging
Guoxing Wan, Lihua Ji, Wenbin Xia, Lan Cheng, Yonggang Zhang
Neutrophil‑to‑lymphocyte ratio (NLR) is commonly considered a useful prognostic index for many cardiovascular diseases; however, it has limited sensitivity and specificity. Factors associated with elevated NLR may aid in the prediction of prognosis with heart failure (HF) in combination with NLR. The present study sought to identify decisive factors associated with NLR in HF patients and investigate their association with elevated NLR. The gene expression profile for blood samples from 197 individuals with chronic heart failure (CHF), with corresponding hematological parameters and clinical data were obtained from the public database, GSE77343...
June 5, 2018: Molecular Medicine Reports
Sohel Shamsuzzaman, Melda Onal, Hillary C St John, J Wesley Pike
Receptor activator of NF-κB ligand (RANKL) is a TNF-like cytokine which mediates diverse physiological functions including bone remodeling and immune regulation. RANKL has been identified in atherosclerotic lesions; however, its role in atherosclerotic plaque development remains elusive. An enhancer located 75 kb upstream of the murine Rankl gene's transcription start site designated D5 is important for its calciotropic hormone- and cytokine-mediated expression. Here, we determined the impact of RANKL levels in atherosclerotic plaque development in the D5 enhancer-null (D5-/- ) mice in an atherogenic Apoe-/- background fed a high-fat diet (HFD)...
December 2017: Journal of Cellular Biochemistry
D Patel, G Gorelik, B Richardson
OBJECTIVE: Lupus develops when genetically predisposed people encounter certain drugs or environmental agents causing oxidative stress such as infections and sun exposure, and then typically follows a chronic relapsing course with flares triggered by the exogenous stressors. Current evidence indicates that these environmental agents can trigger lupus flares by inhibiting the replication of DNA methylation patterns during mitosis in CD4(+) T cells, altering the expression of genes suppressed by this mechanism that convert normal "helper" cells into auto reactive cells which promote lupus flares...
December 2016: Lupus (Los Angeles)
Romana Meletta, Roger Slavik, Linjing Mu, Zoran Rancic, Nicole Borel, Roger Schibli, Simon M Ametamey, Stefanie D Krämer, Adrienne Müller Herde
INTRODUCTION: Endarterectomized human atherosclerotic plaques are a valuable basis for gene expression studies to disclose novel imaging biomarkers and therapeutic targets, such as the cannabinoid receptor type 2 (CB2). In this work, CB2 is expressed on activated immune cells, which are abundant in inflamed plaques. We evaluated the CB2-specific radiotracer [11 C]RS-016 for imaging vascular inflammation in human and mouse atherosclerotic lesions. METHODS: The differential gene expression of microscopically classified human carotid plaques was evaluated using quantitative polymerase chain reaction...
April 2017: Nuclear Medicine and Biology
Mohammadreza Yazdani, Shahdad Khosropanah, Ahmad Hosseini, Mehrnoosh Doroudchi
BACKGROUND: Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown. OBJECTIVE: To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis. METHODS: Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 non-diabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease confirmed by angiography...
December 2016: Iranian Journal of Immunology: IJI
Miguel Hueso, Laura De Ramon, Estanislao Navarro, Elia Ripoll, Josep M Cruzado, Josep M Grinyo, Joan Torras
Data presented in this Data in Brief article correspond to the article "in vivo" silencing of CD40 reduces progression of experimental atherogenesis through a NFκB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis" (M. Hueso, L. De Ramon, E. Navarro, E. Ripoll, J.M. Cruzado, J.M. Grinyo, J. Torras, 2016) [1]. Here, we describe the validation of the silencing of CD40 expression with a specific siRNA in ApoE(-/-) mouse aortas, and its systemic effects on splenic lymphocytic subpopulations as well as on the infiltration of aortic intima by F4/80(+), galectin-3(+) macrophages or by NF-κB(+) cells...
December 2016: Data in Brief
David M Sawyer, Lauren A Pace, Crissey L Pascale, Alexander C Kutchin, Brannan E O'Neill, Robert M Starke, Aaron S Dumont
BACKGROUND: Intracranial aneurysms (IA) are increasingly recognized as a disease driven by chronic inflammation. Recent research has identified key mediators and processes underlying IA pathogenesis, but mechanistic understanding remains incomplete. Lymphocytic infiltrates have been demonstrated in patient IA tissue specimens and have also been shown to play an important role in abdominal aortic aneurysms (AAA) and related diseases such as atherosclerosis. However, no study has systematically examined the contribution of lymphocytes in a model of IA...
July 14, 2016: Journal of Neuroinflammation
Christine Baumgartner, Johanna Brandl, Götz Münch, Martin Ungerer
Animal models of atherosclerosis often present limitations of transferability, since important hallmarks of human disease are not completely reproduced in other species. Rabbits have been used in several approaches: 1) inbred strains: Watanabe hereditary hyperlipidemic animals which express a defect in the LDL receptor, 2) transgenic rabbits, which overexpress human lipoproteins, and first knock-out rabbits. 3) native New Zealand white rabbits (NZW) fed with cholesterol-rich diet for at least 8 weeks represent the quickest way to establish arteriosclerosis...
July 2016: Progress in Biophysics and Molecular Biology
Michael E Reschen, Da Lin, Anil Chalisey, Elizabeth J Soilleux, Christopher A O'Callaghan
BACKGROUND AND AIMS: Coronary artery disease (CAD) risk is associated with non-coding genetic variants at the phosphatase and actin regulating protein 1(PHACTR1) gene locus. The PHACTR1 gene encodes an actin-binding protein with phosphatase regulating activity. The mechanism whereby PHACTR1 influences CAD risk is unknown. We hypothesized that PHACTR1 would be expressed in human cell types relevant to CAD and regulated by atherogenic or genetic factors. METHODS AND RESULTS: Using immunohistochemistry, we demonstrate that PHACTR1 protein is expressed strongly in human atherosclerotic plaque macrophages, lipid-laden foam cells, adventitial lymphocytes and endothelial cells...
July 2016: Atherosclerosis
Giulia Salazar, Chiara Bellocchi, Katia Todoerti, Federica Saporiti, Luca Piacentini, Raffaella Scorza, Gualtiero I Colombo
Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression and production of different inflammatory proteins. ECV-304 endothelial cells were stimulated with IL-1β 100U/ml in the presence or absence of Aminaphtone 6μg/ml. Gene expression profiles were compared at 1, 3, and 6h after stimulation by microarray...
July 5, 2016: European Journal of Pharmacology
Daniel Engelbertsen, Amanda C Foks, Noah Alberts-Grill, Felicia Kuperwaser, Tao Chen, James A Lederer, Petr Jarolim, Nir Grabie, Andrew H Lichtman
OBJECTIVE: Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. APPROACH AND RESULTS: We demonstrate that CD25(+) ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr(-/-)rag1(-/-) mice...
December 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
Andrew T Hale, Chris T Longenecker, Ying Jiang, Sara M Debanne, Danielle E Labatto, Norma Storer, Anne Hamik, Grace A McComsey
OBJECTIVE: To determine the relationships between Krüppel-like factors (KLF) 2 and 4, immune-activation, and subclinical vascular disease in HIV-infected patients on antiretroviral therapy (ART). DESIGN: Double-blind, randomized, placebo-controlled trial. METHODS: We studied 74 HIV-infected adults on ART enrolled in a randomized clinical trial of statin therapy. KLF2 and KLF4 gene expression was measured by quantitative PCR from peripheral blood mononuclear cells (PBMCs) at baseline and after 24 weeks of 10 mg daily rosuvastatin or placebo...
August 24, 2015: AIDS
Fu Sang Luk, Roy Y Kim, Kang Li, Daniel Ching, David K Wong, Sunil K Joshi, Isabella Imhof, Norman Honbo, Holly Hoover, Bo-Qing Zhu, David H Lovett, Joel S Karliner, Robert L Raffai
AIMS: We recently reported that immunosuppression with FTY720 improves cardiac function and extends longevity in Hypomorphic ApoE mice deficient in scavenger receptor Type-BI expression, also known as the HypoE/SR-BI(–/–) mouse model of diet-induced coronary atherosclerosis and myocardial infarction (MI). In this study, we tested the impact of FTY720 on cardiac dysfunction in HypoE/SR-BI(–/–) mice that survive MI and subsequently develop chronic heart failure. METHODS/RESULTS: HypoE/SR-BI(–/–) mice were bred to Mx1-Cre transgenic mice, and offspring were fed a high-fat diet (HFD) for 3...
January 2016: Journal of Cardiovascular Pharmacology
Natalia I Dmitrieva, Maurice B Burg
Cardiovascular diseases (CVDs) are a leading health problem worldwide. Epidemiologic studies link high salt intake and conditions predisposing to dehydration such as low water intake, diabetes and old age to increased risk of CVD. Previously, we demonstrated that elevation of extracellular sodium, which is a common consequence of these conditions, stimulates production by endothelial cells of clotting initiator, von Willebrand Factor, increases its level in blood and promotes thrombogenesis. In present study, by PCR array, using human umbilical vein endothelial cells (HUVECs), we analyzed the effect of high NaCl on 84 genes related to endothelial cell biology...
2015: PloS One
Gregg J Silverman
During murine immune development, recurrent B cell clones arise in a predictable fashion. Among these B cells, an archetypical clonotypic set that recognizes phosphorylcholine (PC) antigens and produces anti-PC IgM, first implicated for roles in microbial protection, was later found to become expanded in hyperlipidemic mice and in response to an increased in vivo burden of apoptotic cells. These IgM natural antibodies can enhance clearance of damaged cells and induce intracellular blockade of inflammatory signaling cascades...
December 2015: Annals of the New York Academy of Sciences
Maria Grandoch, Kathrin Feldmann, Joachim R Göthert, Lena S Dick, Susanne Homann, Christina Klatt, Julia K Bayer, Jan N Waldheim, Berit Rabausch, Nadine Nagy, Alexander Oberhuber, René Deenen, Karl Köhrer, Stefan Lehr, Bernhard Homey, Klaus Pfeffer, Jens W Fischer
RATIONALE: Lymphotoxin β receptor (LTbR) regulates immune cell trafficking and communication in inflammatory diseases. However, the role of LTbR in atherosclerosis is still unclear. OBJECTIVE: The aim of this study was to elucidate the role of LTbR in atherosclerosis. METHODS AND RESULTS: After 15 weeks of feeding a Western-type diet, mice double-deficient in apolipoprotein E and LTbR (apoE(-/-)/LTbR(-/-)) exhibited lower aortic plaque burden than did apoE(-/-) littermates...
April 10, 2015: Circulation Research
Nuria Barbarroja, Carlos Pérez-Sanchez, Patricia Ruiz-Limon, Carmen Castro-Villegas, Maria Angeles Aguirre, Rosario Carretero, Pedro Segui, Yolanda Jimenez-Gomez, Manuela Sanna, Antonio Rodriguez-Ariza, Eduardo Collantes-Estevez, Alejandro Escudero, Chary López-Pedrera
OBJECTIVE: Previous studies have suggested a relationship between anticyclic citrullinated protein (CCP) levels and development of cardiovascular disease in rheumatoid arthritis (RA). However, a limited number of studies have demonstrated an involvement of anti-CCPs in those processes. This study was aimed to define the specific role of these auto-antibodies in the pro-oxidative, inflammatory, and proatherogenic profile observed in leukocytes from RA patients. APPROACH AND RESULTS: Seventy-five RA patients and 31 healthy donors were enrolled...
December 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Katarzyna Konieczka, Robert Ritch, Carlo Enrico Traverso, Dong Myung Kim, Michael Scott Kook, Augusto Gallino, Olga Golubnitschaja, Carl Erb, Herbert A Reitsamer, Teruyo Kida, Natalia Kurysheva, Ke Yao
The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma...
2014: EPMA Journal
Carlota Recio, Ainhoa Oguiza, Iolanda Lazaro, Beñat Mallavia, Jesus Egido, Carmen Gomez-Guerrero
OBJECTIVE: Activation of Janus kinase/signal transducers and activators of transcription (STAT) pathway by hyperglycemia and dislypidemia contributes to the progression of diabetic complications, including atherosclerosis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate Janus kinase/STAT and have emerged as promising target for anti-inflammatory therapies. We investigated whether a cell-permeable lipopeptide corresponding to the kinase inhibitory region of SOCS1 could reduce atherosclerosis in diabetic mice and identified the mechanisms involved...
September 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
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