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Gene expression in lymphocytes and atherosclerosis

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...
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
Jinhee Kim, Nima Ghasemzadeh, Danny J Eapen, Neo Christopher Chung, John D Storey, Arshed A Quyyumi, Greg Gibson
BACKGROUND: Genetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death. METHODS: Peripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2...
2014: Genome Medicine
Nicholas S Kirkby, Martina H Lundberg, William R Wright, Timothy D Warner, Mark J Paul-Clark, Jane A Mitchell
Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE(-/-)/COX-2(-/-) mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release...
2014: PloS One
Dennis Wolf, Felix Jehle, Nathaly Anto Michel, Eva Nora Bukosza, Jennifer Rivera, Yung Chih Chen, Natalie Hoppe, Bianca Dufner, Alexandra Ortiz Rodriguez, Christian Colberg, Leandro Nieto, Benjamin Rupprecht, Ansgar Wiedemann, Lisa Schulte, Alexander Peikert, Nicole Bassler, Andrey Lozhkin, Sonja Patricia Hergeth, Peter Stachon, Ingo Hilgendorf, Florian Willecke, Constantin von Zur Mühlen, Dominik von Elverfeldt, Christoph J Binder, Peter Aichele, Nerea Varo, Mark A Febbraio, Peter Libby, Christoph Bode, Karlheinz Peter, Andreas Zirlik
BACKGROUND: Costimulatory cascades such as the CD40L-CD40 dyad enhance immune cell activation and inflammation during atherosclerosis. Here, we tested the hypothesis that CD40 directly modulates traits of the metabolic syndrome in diet-induced obesity in mice. METHODS AND RESULTS: To induce the metabolic syndrome, wild-type or CD40(-/-) mice consumed a high-fat diet for 20 weeks. Unexpectedly, CD40(-/-) mice exhibited increased weight gain, impaired insulin secretion, augmented accumulation of inflammatory cells in adipose tissue, and enhanced proinflammatory gene expression...
June 10, 2014: Circulation
Susanne Dihlmann, Philipp Erhart, Arianeb Mehrabi, Arash Nickkholgh, Felix Lasitschka, Dittmar Böckler, Maani Hakimi
Chronic vascular inflammation is a key hallmark in the pathogenesis of abdominal aortic aneurysm (AAA). Recent investigations have suggested that the inflammasome, a cytosolic multiprotein complex that recognizes pathogen-associated molecular patterns, plays a role in atherosclerosis. However, its role in AAA inflammation has not yet been investigated. This pilot study analyzed inflammasome activation and its intramural localization in 24 biopsy samples from 11 patients with asymptomatic AAA versus 12 aortic samples from apparently healthy controls...
2014: Molecular Medicine
Kirsten B Holven, Ingunn Narverud, Henriette W Lindvig, Bente Halvorsen, Gisle Langslet, Marit S Nenseter, Stine M Ulven, Leiv Ose, Pål Aukrust, Kjetil Retterstøl
OBJECTIVE: The atherosclerotic process is driven by elevated Low-density lipoprotein (LDL)-cholesterol in combination with enhanced inflammatory responses. Several mediators participate in this complex inflammatory network including members of the tumour necrosis factor (receptor) superfamily. Familial hypercholesterolemia (FH) is associated with increased risk of developing premature atherosclerosis. Statin treatment may normalize LDL-cholesterol levels, but it is not known if the inflammatory responses are normalized in statin-treated FH patients...
April 2014: Atherosclerosis
Mukesh K Jain, Panjamaporn Sangwung, Anne Hamik
This invited review summarizes work presented in the Russell Ross lecture delivered at the 2012 proceedings of the American Heart Association. We begin with a brief overview of the structural, cellular, and molecular biology of Krüppel-like factors. We then focus on discoveries during the past decade, implicating Krüppel-like factors as key determinants of vascular cell function in atherosclerotic vascular disease.
March 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Kazuo Yamagata, Chiaki Tusruta, Akane Ohtuski, Motoki Tagami
Docosahexaenoic acid (DHA) prevents atherosclerosis and may decrease monocyte/macrophage activation by tumor necrosis factor (TNF)-α. Here, we sought to determine the protective effects of DHA against TNF-α-induced stimulation of lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) expression, which is associated with atherosclerosis. Using reverse transcription polymerase chain reaction, we found that TNF-α induced the expression of LOX-1 (OLR1), NADPH oxidase 2 (Nox2), p47phox (NCF1), very late antigen-4 (ITGA4), and lymphocyte function-associated antigen (ITGAL) genes...
April 2014: Prostaglandins, Leukotrienes, and Essential Fatty Acids
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