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Gene expression in peripheral blood in stroke

Grant C O'Connell, Madison B Treadway, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution of the ten genes across the peripheral immune system by measuring their expression levels on isolated neutrophils, monocytes, B-lymphocytes, CD-4+ T-lymphocytes, CD-8+ T-lymphocytes, and NK-cells generated from the blood of healthy donors (n = 3)...
March 17, 2018: Translational Stroke Research
Berk Arapi, Burcu Bayoğlu, Müjgan Cengiz, Ahmet Dirican, Serkan Burç Deser, Yerik Junusbekov, Caner Arslan
BACKGROUND: Carotid artery stenosis (CAS) is the atherosclerotic narrowing of the proximal internal carotid artery (ICA) and one of the main causes of stroke. Elevated expression of the pleiotropic proinflammatory cytokine, interleukin-18 (IL18), has been shown in human atherosclerotic plaques. AIMS: To investigate whether IL18 and interleukin-18 binding protein (IL18BP) mRNA expression and IL18 -137 G/C (rs187238) variants are associated with CAS development. STUDY DESIGN: Case-control study...
February 27, 2018: Balkan Medical Journal
Mika Takarada-Iemata, Akifumi Yoshikawa, Hieu Minh Ta, Nahoko Okitani, Takumi Nishiuchi, Yasuhiro Aida, Tomoya Kamide, Tsuyoshi Hattori, Hiroshi Ishii, Takashi Tamatani, Thuong Manh Le, Jureepon Roboon, Yasuko Kitao, Tomohiro Matsuyama, Mitsutoshi Nakada, Osamu Hori
Disruption of the blood-brain barrier (BBB) following cerebral ischemia is closely related to the infiltration of peripheral cells into the brain, progression of lesion formation, and clinical exacerbation. However, the mechanism that regulates BBB integrity, especially after permanent ischemia, remains unclear. Here, we present evidence that astrocytic N-myc downstream-regulated gene 2 (NDRG2), a differentiation- and stress-associated molecule, may function as a modulator of BBB permeability following ischemic stroke, using a mouse model of permanent cerebral ischemia...
February 24, 2018: Glia
James A Wingrove, Karen Fitch, Brian Rhees, Steven Rosenberg, Deepak Voora
BACKGROUND: Cardiovascular disease and its sequelae are major causes of global mortality, and better methods are needed to identify patients at risk for future cardiovascular events. Gene expression analysis can inform on the molecular underpinnings of risk factors for cardiovascular events. Smoking and aspirin have known opposing effects on platelet reactivity and MACE, however their effects on each other and on MACE are not well described. METHODS: We measured peripheral blood gene expression levels of ITGA2B, which is upregulated by aspirin and correlates with platelet reactivity on aspirin, and a 5 gene validated smoking gene expression score (sGES) where higher expression correlates with smoking status, in participants from the previously reported PREDICT trial (NCT 00500617)...
January 12, 2018: BMC Medical Genomics
Mihoko Kurano, Sahar Ghavidel Darestani, Atsushi Shinnakasu, Kiyoaki Yamamoto, Yukari Dochi, Kayo Uemura, Yuko Ikeda, Akira Kikuchi, Hiroshi Hashiguchi, Takahisa Deguchi, Yoshihiko Nishio
AIMS: Renal dysfunction in addition to diabetes is a serious risk factor for cardiovascular events. We hypothesized that some of the changes in gene expression in blood cells cause renal dysfunction and macrovascular disease through impaired endothelial function. This study aimed to define which changes in gene expression in peripheral blood mononuclear cells (PBMCs) are related to renal function parameters and endothelial function of large arteries in patients with type 2 diabetes mellitus (T2DM)...
December 13, 2017: Diabetes Research and Clinical Practice
George D Vavougios, Sotirios G Zarogiannis, Karen Angeliki Krogfelt, Konstantinos Gourgoulianis, Dimos Dimitrios Mitsikostas, Georgios Hadjigeorgiou
BACKGROUND: currently only 4 studies have explored the potential role of PARK7's dysregulation in MS pathophysiology Currently, no study has evaluated the potential role of the PARK7 interactome in MS. OBJECTIVE: The aim of our study was to assess the differential expression of PARK7 mRNA in peripheral blood mononuclears (PBMCs) donated from MS versus healthy patients using data mining techniques. METHODS: The PARK7 interactome data from the GDS3920 profile were scrutinized for differentially expressed genes (DEGs); Gene Enrichment Analysis (GEA) was used to detect significantly enriched biological functions...
October 24, 2017: Multiple Sclerosis and related Disorders
Grant C O'Connell, Madison B Treadway, Ashley B Petrone, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Background: The use of reference genes for normalization of whole blood qRT-PCR data may be problematic in conditions such as stroke which induce alterations in white blood cell differential. In this study, we assessed the influence of stroke on the stability of commonly employed reference genes, and we evaluated data-driven normalization as an alternative. Methods: Peripheral whole blood was sampled from 33 stroke patients and 29 controls, and qRT-PCR was used to measure the expression levels of 10 target genes whose transcripts are known stroke biomarkers...
November 8, 2017: Laboratory Medicine
Grażyna Janikowska, Aleksandra Żebrowska, Aleksandra Kochańska-Dziurowicz, Urszula Mazurek
BACKGROUND: Regular and moderate exercise is beneficial for improving the efficiency of the heart, but high-intensity physical activity may result in cardiac changes. OBJECTIVES: This study focuses on the identification of the differences in echocardiography and blood variables before exercise, as well as the genes associated with cardiac hypertrophy at rest and in response to graded exercise test. MATERIAL AND METHODS: The study group was made up of 28 road cyclists...
September 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Connor A Emdin, Amit V Khera, Derek Klarin, Pradeep Natarajan, Seyedeh M Zekavat, Akihiro Nomura, Mary Haas, Krishna Aragam, Diego Ardissino, James G Wilson, Heribert Schunkert, Ruth McPherson, Hugh Watkins, Roberto Elosua, Matthew J Bown, Nilesh J Samani, Usman Baber, Jeanette Erdmann, Padhraig Gormley, Aarno Palotie, Nathan O Stitziel, Namrata Gupta, John Danesh, Danish Saleheen, Stacey Gabriel, Sekar Kathiresan
BACKGROUND: Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of the nitric oxide pathway as a therapeutic strategy. METHODS: We analyzed the association of common and rare genetic variants in 2 genes that mediate nitric oxide signaling (Nitric Oxide Synthase 3 [ NOS3 ] and Guanylate Cyclase 1, Soluble, Alpha 3 [ GUCY1A3 ]) with a range of human phenotypes...
January 16, 2018: Circulation
Nathalie Kubis
The first clinical trials of cell therapy in stroke were first published in the 2000s and consisted of neural stems cells transplanted via the intracerebral pathway. Since mesenchymal stem cells showed similar capacities to differentiate into neural cells and allowed autologous cell transplantation, they were then preferentially studied, including diabetes and hypertension. More recently, bone marrow derived mononuclear cells were successfully transplanted in stroke with no need of culture processing, and simple collection by density gradient centrifugation rendering them immediately ready for use...
2017: Keio Journal of Medicine
Grant C O'Connell, Paul D Chantler, Taura L Barr
Our group recently employed genome-wide transcriptional profiling in tandem with machine-learning based analysis to identify a ten-gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population. Publicly available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 h post-symptom onset, as well from 23 cardiovascular disease controls, were obtained via the National Center for Biotechnology Information Gene Expression Omnibus...
December 2017: Genomics Data
Kaihua Zhai, Xiangli Kong, Boyu Liu, Jiyu Lou
This study aimed to identify the key differentially expressed genes (DEGs) following ischemic stroke (IS).The GSE22255 microarray dataset, which contains samples from peripheral blood mononuclear cells of 20 IS patients and 20 sex- and age-matched controls, was downloaded from the Gene Expression Omnibus. After data pre-processing, DEGs were identified using the Linear Models for Microarray Data package in R. The Search Tool for the Retrieval of Interacting Genes database was used to predict the interactions among the products of DEGs, and then Cytoscape software was used to visualize the protein-protein interaction (PPI) network...
August 2017: Medicine (Baltimore)
Annabel J Sorby-Adams, Amanda M Marcoionni, Eden R Dempsey, Joshua A Woenig, Renée J Turner
Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke...
August 17, 2017: International Journal of Molecular Sciences
Fuhai Song, Ying Qian, Xing Peng, Xiuhui Li, Peiqi Xing, Dongqing Ye, Hongxing Lei
Peripheral blood is an attractive source for the discovery of disease biomarkers. Gene expression profiling of whole blood or its components has been widely conducted for various diseases. However, due to population heterogeneity and the dynamic nature of gene expression, certain biomarkers discovered from blood transcriptome studies could not be replicated in independent studies. In the meantime, it's also important to know whether a reliable biomarker is shared by several diseases or specific to certain health conditions...
2017: PloS One
Nils Schallner, Judith-Lisa Lieberum, David Gallo, Robert H LeBlanc, Patrick M Fuller, Khalid A Hanafy, Leo E Otterbein
BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is associated with a temporal pattern of stroke incidence. We hypothesized that natural oscillations in gene expression controlling circadian rhythm affect the severity of neuronal injury. We moreover predict that heme oxygenase-1 (HO-1/Hmox1) and its product carbon monoxide (CO) contribute to the restoration of rhythm and neuroprotection. METHODS: Murine SAH model was used where blood was injected at various time points of the circadian cycle...
September 2017: Stroke; a Journal of Cerebral Circulation
Zhibin Li, Fang Yu, Xiaoqing Zhou, Sian Zeng, Qiong Zhan, Mei Yuan, Qidong Yang, Yunhai Liu, Jian Xia
BACKGROUND AND AIMS: microRNA223 (miR-223) plays an important role in the development of atherosclerosis and ischemic stroke. It is involved in regulation of multiple physiological and pathophysiological processes such as cholesterol metabolism, endothelial cell (EC) function, and thrombosis. Here we investigated the role of methylation regulation of MIR-223 promoter region in atherosclerotic cerebral infarction (ACI) patients. METHODS: A total of 23 patients with ACI and 32 healthy individuals were recruited...
June 28, 2017: Atherosclerosis
Ming Sang, Xuanbin Wang, Hanyao Zhang, Xiaodong Sun, Xudong Ding, Puqing Wang, Rong Jiao, Huaxian Cheng, Sijun Yang, Guibin Zhang
RNA-sequencing, a powerful tool, yields a comprehensive view of whole transcriptome. Intracerebral hemorrhage (ICH) is a devastating form of stroke. To date, RNA-sequencing analysis of ICH has not been reported. Peripheral blood mononuclear cells (PBMCs) were used as a source of mRNA for gene expression profile analysis in stroke. In this study, we performed transcriptome analyses for PBMCs from four ICH patients and four healthy volunteers on Illumina platform. We identified 4040 significantly differentially expressed genes (DEGs)...
August 2017: DNA and Cell Biology
Kelly M DeMars, Changjun Yang, Kimberly E Hawkins, Austin O McCrea, David M Siwarski, Eduardo Candelario-Jalil
P-glycoprotein (P-gp) is known to transport a diverse array of xenobiotics, including therapeutic drugs. A member of the ATP-binding cassette (ABC) transporter family, P-gp is a protein encoded by the gene Mdr1 in humans and Abcb1 in rodents (represented by 2 isoforms Abcb1a and Abcb1b). Lining the luminal and abluminal membrane of brain capillary endothelial cells, P-gp is a promiscuous efflux pump extruding a variety of exogenous toxins and drugs. In this study, we measured dynamic changes in Abcb1a and Abcb1b transcripts and P-gp protein in the brain, liver, and kidney after experimental stroke...
2017: Journal of Experimental Neuroscience
Grant C O'Connell, Madison B Treadway, Ashley B Petrone, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging...
April 26, 2017: Scientific Reports
Ashley B Petrone, Valerie Gionis, Richard Giersch, Taura L Barr
BACKGROUND: In 2010, there were approximately 2.2 million emergency room visits associated with traumatic brain injury (TBI), with 80 percent diagnosed as mild TBI or concussion. In addition, there are a large number of TBIs, especially mild TBIs, which go either unreported by patients or initially undiagnosed by clinicians. Our team has previously identified a panel of immune-related genes that can diagnose ischemic stroke at triage, and due to shared pathophysiological mechanisms of TBI and stroke, we hypothesized that this panel of genes may also be utilized for the diagnosis of TBI...
February 10, 2017: NeuroRehabilitation
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