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Peripheral blood gene expression in human ischemic stroke

Candela Diaz-Cañestro, Mario Merlini, Nicole R Bonetti, Luca Liberale, Patricia Wüst, Sylvie Briand-Schumacher, Jan Klohs, Sara Costantino, Melroy Miranda, Gabriele Schoedon-Geiser, Gerd A Kullak-Ublick, Alexander Akhmedov, Francesco Paneni, Jürg H Beer, Thomas F Lüscher, Giovanni G Camici
BACKGROUND: In acute ischemic stroke (AIS) patients, impaired blood-brain barrier (BBB) integrity is associated with hemorrhagic transformation and worsened outcome. Yet, the mechanisms underlying these relationships are poorly understood and consequently therapeutic strategies are lacking. This study sought to determine whether SIRT5 contributes to BBB damage following I/R brain injury. METHODS AND RESULTS: SIRT5 knockout (SIRT5-/- ) and wild type (WT) mice underwent transient middle cerebral artery (MCA) occlusion (tMCAO) followed by 48h of reperfusion...
June 1, 2018: International Journal of Cardiology
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
Yingying Wang, Yunpeng Cai
Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages...
2016: Scientific Reports
Mateusz G Adamski, Yan Li, Erin Wagner, Hua Yu, Chloe Seales-Bailey, Helen Durkin, Qing Hao, Steven A Soper, Michael Murphy, Alison E Baird
T lymphocytes may play an important role in the evolution of ischemic stroke. Depletion of γδT cells has been found to abrogate ischemia reperfusion injury in murine stroke. However, the role of γδT cells in human ischemic stroke is unknown. We aimed to determine γδT cell counts and γδT cell interleukin 17A (IL-17A) production in the clinical setting of ischemic stroke. We also aimed to determine the associations of γδT cell counts with ischemic lesion volume, measures of clinical severity and with major stroke risk factors...
2014: PloS One
Z-L Zhang, W-C Wu, J-Q Liu, Y-B Yao, M-D Pan, C-B Yang, J-G Wang, X-W Huang, J-Y Lin
BACKGROUND: Prognostic blood biomarkers in the setting of acute ischemic stroke have become increasingly relevant for risk stratification, monitoring disease and response to therapies, developing targets for neuroprotective treatment and as surrogate end points for treatment trials. AIM: We aim to find the feature genes which can accurately detect acute ischemic stroke and perform function analysis of these crucial genes in peripheral blood mononuclear cells. MATERIALS AND METHODS: The gene expression profile GSE22255 was downloaded from Gene Expression Omnibus (GEO) database which includes 20 ischemic stroke patients and 20 controls...
2014: European Review for Medical and Pharmacological Sciences
Z Meng, M Li, Q He, S Jiang, X Zhang, J Xiao, Y Bai
Neuropathologic processes such as cerebral ischemia can enhance neurogenesis. Angiopoietin-1 (Ang1) emerges as a critical regulator of physiological and pathological angiogenesis during embryonic and postnatal life. Although Ang1 could protect peripheral vasculature from vascular leakage following ischemic injury, the role of Ang1 in long-term neurological recovery after ischemic stroke remains elusive. This study aims to examine whether Ang1 overexpression via lentivirus-mediated gene transfer enhances neurovascular remodeling and improves functional outcome in a rat model of focal cerebral ischemia...
May 16, 2014: Neuroscience
Silvia Ferronato, Macarena Gomez-Lira, Marta Menegazzi, Erica Diani, Silvia Olivato, Marianna Sartori, Alberto Scuro, Giovanni Malerba, Pier Franco Pignatti, Maria Grazia Romanelli, Sara Mazzucco
Toll-like receptor-4 (TLR4) is a primary receptor of the innate immune reaction and compelling evidence demonstrates its involvement in the pathogenesis of atherosclerosis and stroke. TLR4 is constitutively expressed on monocytes and endothelial cells; it is highly expressed in atherosclerotic plaques and in peripheral blood of patients after ischemic stroke. Polymorphisms in the promoter region that alter the transcriptional regulation of this gene may represent genetic risk factors involved in the predisposition to atherosclerotic disease...
December 2013: Journal of Human Genetics
Jia Liu, Jun Yan, Judith M Greer, Stephen J Read, Robert D Henderson, Stephen E Rose, Alan Coulthard, Pamela A McCombe
Human adrenomedullin (ADM), a 52-amino acid peptide, belongs to the calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. ADM acts as a multifunctional regulatory peptide and is upregulated in response to hypoxia. Previous microarray studies have found increased ADM gene (ADM) expression in peripheral blood cells of patients with stroke, however, it is unknown if an increased ADM level is correlated with severity of human ischemic stroke. This study investigated ADM expression in peripheral blood leukocytes (PBL) of healthy controls and subjects at day 1, week 1 and week 3 postacute ischemic stroke using rtPCR methodology...
April 2014: International Journal of Neuroscience
Sung Ho Lee, Mukesh Kumar Gupta, Young Tae Ho, Teoan Kim, Hoon Taek Lee
Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein...
September 2013: Poultry Science
Tao Sun, Ji-Peng Zhou, Da-Bin Kuang, Mu-Peng Li, Yan Xiong, Jie Tang, Jian Xia, Yong-Ping Bai, Guo-Ping Yang, Yuan-Jian Li, Xiao-Ping Chen
BACKGROUND: Dimethylarginine dimethylaminohydrolases 1 (DDAH1) is the major enzyme responsible for inactivation of asymmetric dimethylarginine (ADMA). This study seeks to clarify the correlations between mRNA expression levels of DDAH1 transcript variants and the relationship with ADMA metabolizing activity in human. METHODS: The mRNA expression levels of DDAH1 transcript variants in primarily cultured human umbilical vein endothelial cells (HUVECs) and peripheral blood mononuclear cells (PBMCs) from healthy control subjects and patients suffering from both acute ischemic stroke (AIS) and acute myocardial infarction (AMI) were determined by real-time polymerase chain reaction...
December 2013: American Journal of Hypertension
Georgios Koutsis, Gerasimos Siasos, Konstantinos Spengos
MicroRNAs (miRNAs) are small non-coding RNAs approximately 22 nucleotides in length that play a pivotal role in post-transcriptional gene regulation by binding to complementary sites in the 3'-untranslated region of messenger RNAs. In the past decade, their role in several human diseases, from cancer to cardiovascular disease, has been established by a wealth of evidence. Stroke is responsible for 10% of deaths worldwide and is one of the leading causes of disability. MiRNAs are involved in stroke risk factors including hypertension, atherosclerosis, atrial fibrillation, diabetes and dyslipidemia...
2013: Current Topics in Medicinal Chemistry
Dean Wu, Yuan-Chii G Lee, Hsing-Cheng Liu, Rey-Yue Yuan, Hung-Yi Chiou, Chia-Hsiu Hung, Chaur-Jong Hu
OBJECTIVE: Toll-like receptors (TLRs) are important molecules for detecting both pathogen invasion and tissue damage. The expression of TLR4 is upregulated in ischemic stroke, at least in the subacute stage. However, the TLR downstream pathways in the context of stroke have not been well studied in previous research. The purpose of this study is to elucidate the TLR4 downstream pathways following ischemic stroke. DESIGN AND METHODS: In this study, 12 ischemic stroke patients and 12 controls were selected from among 89 ischemic stroke patients and 166 controls...
August 2013: Clinical Biochemistry
Rafael Rodriguez-Mercado, Gregory D Ford, Zhenfeng Xu, Edmundo N Kraiselburd, Melween I Martinez, Vesna A Eterović, Edgar Colon, Idia V Rodriguez, Peter Portilla, Pedro A Ferchmin, Lynette Gierbolini, Maria Rodriguez-Carrasquillo, Michael D Powell, John V K Pulliam, Casey O McCraw, Alicia Gates, Byron D Ford
The goal of this study was to characterize acute neuronal injury in a novel nonhuman primate (NHP) ischemic stroke model by using multiple outcome measures. Silk sutures were inserted into the M1 segment of the middle cerebral artery of rhesus macaques to achieve permanent occlusion of the vessel. The sutures were introduced via the femoral artery by using endovascular microcatheterization techniques. Within hours after middle cerebral artery occlusion (MCAO), infarction was detectable by using diffusion-weighted MRI imaging...
October 2012: Comparative Medicine
Glen C Jickling, Boryana Stamova, Bradley P Ander, Xinhua Zhan, Dazhi Liu, Shara-Mae Sison, Piero Verro, Frank R Sharp
BACKGROUND AND PURPOSE: The cause of ischemic stroke remains unclear, or cryptogenic, in as many as 35% of patients with stroke. Not knowing the cause of stroke restricts optimal implementation of prevention therapy and limits stroke research. We demonstrate how gene expression profiles in blood can be used in conjunction with a measure of infarct location on neuroimaging to predict a probable cause in cryptogenic stroke. METHODS: The cause of cryptogenic stroke was predicted using previously described profiles of differentially expressed genes characteristic of patients with cardioembolic, arterial, and lacunar stroke...
August 2012: Stroke; a Journal of Cerebral Circulation
Seung-Hun Oh, Ok-Joon Kim, Dong-Ah Shin, Jihwan Song, Hanna Yoo, Yu-Kyung Kim, Jin-Kyeoung Kim
OBJECTIVE: Peripheral blood cells and inflammatory mediators have a detrimental effect on brain during cerebral ischemia. We investigated the immunologic changes on peripheral blood in the acute phase of ischemic stroke using RNA microarray. METHODS: mRNA microarray and real time-polymerase chain reaction (RT-PCR) for genes of interest in microarray data were analyzed in 12 stroke patients and 12 controls. Plasma matrix metalloproteinase-9 (MMP-9) concentrations were measured in 120 stroke patients and 82 controls...
August 15, 2012: Journal of Neuroimmunology
Tiago Krug, João Paulo Gabriel, Ricardo Taipa, Benedita V Fonseca, Sophie Domingues-Montanari, Israel Fernandez-Cadenas, Helena Manso, Liliana O Gouveia, João Sobral, Isabel Albergaria, Gisela Gaspar, Jordi Jiménez-Conde, Raquel Rabionet, José M Ferro, Joan Montaner, Astrid M Vicente, Mário Rui Silva, Ilda Matos, Gabriela Lopes, Sofia A Oliveira
We hereby propose a novel approach to the identification of ischemic stroke (IS) susceptibility genes that involves converging data from several unbiased genetic and genomic tools. We tested the association between IS and genes differentially expressed between cases and controls, then determined which data mapped to previously reported linkage peaks and were nominally associated with stroke in published genome-wide association studies. We first performed gene expression profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls...
June 2012: Journal of Cerebral Blood Flow and Metabolism
Tzu-Hsien Tsai, Yung-Lung Chen, Hung-Sheng Lin, Chu-Feng Liu, Hsuen-Wen Chang, Cheng-Hsien Lu, Wen-Neng Chang, Shu-Feng Chen, Chiung-Jen Wu, Steve Leu, Sheung-Fat Ko, Hon-Kan Yip
AIM: To evaluate the potential of the lipoprotein-associated phospholipase A(2) (Lp-PLA(2) level as a biomarker in the prediction of prognostic outcome in patients with acute ischemic stroke (IS). METHODS: From October 2008 to March 2010, 130 patients with acute IS were prospectively enrolled in the study and their medical records were reviewed. A blood sample was collected from each patient 48 hours after acute IS, as well as from 20 healthy volunteers as controls...
2012: Journal of Atherosclerosis and Thrombosis
Reyna L VanGilder, Jason D Huber, Charles L Rosen, Taura L Barr
The molecular causality and response to stroke is complex. Yet, much of the literature examining the molecular response to stroke has focused on targeted pathways that have been well-characterized. Consequently, our understanding of stroke pathophysiology has made little progress by way of clinical therapeutics since tissue plasminogen activator was approved for treatment nearly a decade ago. The lack of clinical translation is in part due to neuron-focused studies, preclinical models of cerebral ischemia and the paradoxical nature of neuro-inflammation...
July 1, 2012: Brain Research Bulletin
Lasse Folkersen, Jonas Persson, Johan Ekstrand, Hanna E Agardh, Göran K Hansson, Anders Gabrielsen, Ulf Hedin, Gabrielle Paulsson-Berne
Classic risk factors, including age, smoking, serum cholesterol, diabetes and blood pressure, constitute the basis of present risk prediction models but fail to identify all individuals at risk. The objective of this study was to investigate if genomic and transcriptional patterns improve prediction of ischemic events in patients with established carotid artery disease. Genotype and gene expression profiles were obtained from carotid plaque tissue (n = 126) and peripheral blood mononuclear cells (n = 97) of patients undergoing carotid endarterectomy...
2012: Molecular Medicine
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