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https://www.readbyqxmd.com/read/28634421/the-role-of-von-willebrand-factor-in-vascular-inflammation-from-pathogenesis-to-targeted-therapy
#1
REVIEW
Felice Gragnano, Simona Sperlongano, Enrica Golia, Francesco Natale, Renatomaria Bianchi, Mario Crisci, Fabio Fimiani, Ivana Pariggiano, Vincenzo Diana, Andreina Carbone, Arturo Cesaro, Claudia Concilio, Giuseppe Limongelli, Mariagiovanna Russo, Paolo Calabrò
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28623120/association-between-ischemic-stroke-and-erdheim-chester-disease-a-case-report-and-review-of-literature
#2
Guillaume Fargeot, Sabrina Stefanizzi, Sebastien Depuydt, Frederic Klapczynski, Alain Ameri
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by a xanthogranulomatous infiltration of tissues by spumous histiocytes. Neurological involvement is frequent, but ischemic strokes have been exceptionally described. We report the case of a 68-year-old woman who presented with an acute ischemic stroke associated with a multisystemic disorder including insipidus diabetes, infiltration of the aorta and the carotid arteries, perirenal infiltration, aortitis, and lytic bone lesions...
June 13, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28609584/endothelial-nitric-oxide-synthase-inhibition-triggers-inflammatory-responses-in-the-brain-of-male-rats-exposed-to-ischemia-reperfusion-injury
#3
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Fabio Blandini, Diana Amantea, Cristina Tassorelli
Nitric oxide (NO) derived from endothelial NO synthase (eNOS) plays a role in preserving and maintaining the brain's microcirculation, inhibiting platelet aggregation, leukocyte adhesion, and migration. Inhibition of eNOS activity results in exacerbation of neuronal injury after ischemia by triggering diverse cellular mechanisms, including inflammatory responses. To examine the relative contribution of eNOS in stroke-induced neuroinflammation, we analyzed the effects of systemic treatment with l-N-(1-iminoethyl)ornithine (L-NIO), a relatively selective eNOS inhibitor, on the expression of MiR-155-5p, a key mediator of innate immunity regulation and endothelial dysfunction, in the cortex of male rats subjected to transient middle cerebral artery occlusion (tMCAo) followed by 24 hr of reperfusion...
June 13, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28606360/sex-differences-in-regulatory-cells-in-experimental-stroke
#4
Hilary A Seifert, Gil Benedek, Jian Liang, Ha Nguyen, Gail Kent, Arthur A Vandenbark, Julie A Saugstad, Halina Offner
Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19(+)CD5(+)CD1d(hi) B10 cells as well as anti-inflammatory CD11b(+)CD206(+) microglia/macrophages in the ipsilateral vs...
June 8, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#5
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28580536/annexin-a2-plus-low-dose-tissue-plasminogen-activator-combination-attenuates-cerebrovascular-dysfunction-after-focal-embolic-stroke-of-rats
#6
Xiang Fan, Yinghua Jiang, Zhanyang Yu, Qi Liu, Shuzhen Guo, Xiaochuan Sun, Klaus van Leyen, MingMing Ning, Xiumei Gao, Eng H Lo, Xiaoying Wang
Previous studies showed recombinant annexin A2 (rA2) in combination with low-dose tissue-type plasminogen activator (tPA) improved thrombolytic efficacy and long-term neurological outcomes after embolic focal ischemia in rats. The objective of this study was to investigate the effects and mechanisms of the combination in early BBB integrity and cerebrovascular patency in the rat focal embolic stroke model. Ischemic brain infarct volume and hemorrhagic transformation were quantified at 24 h after stroke. At an earlier time point, 16 h after stroke, BBB integrity was evaluated by IgG extravasation, and the involved mechanisms were assessed for tight junction ZO-1 and adhesion junction ve-cadherin protein expression, matrix metalloproteinase activation, extracellular matrix collagen IV and endothelial barrier antigen expression, and activation of microglia/macrophages and astrocytes...
June 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28559142/ag1296-enhances-plaque-stability-via-inhibiting-inflammatory-responses-and-decreasing-mmp-2-and-mmp-9-expression-in-apoe-mice
#7
Min Dong, Changping Zhou, Liang Ji, Bing Pan, Lemin Zheng
BACKGROUND: Atherosclerosis is a chronic process that progresses to unstable plaques. Plaque rupture leads to deleterious consequences such as acute coronary syndrome, thrombosis and stroke. AG1296 is a potent tyrosine kinase inhibitor which is able to block PDGF-PDGFR signaling pathway. This study aims to assess the effect of AG1296 on plaque stability and explore the potential mechanisms. METHODS: Atherosclerotic plaques were induced in carotid arteries in ApoE-/- mice by perivascular collar placement...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28536169/inflammatory-stroke-extracellular-vesicles-induce-macrophage-activation
#8
Yvonne Couch, Naveed Akbar, Simon Davis, Roman Fischer, Alex M Dickens, Ain A Neuhaus, Annette I Burgess, Peter M Rothwell, Alastair M Buchan
BACKGROUND AND PURPOSE: Extracellular vesicles (EVs) are protein-lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs. METHODS: EVs were quantified and analyzed in the sera of patients after an acute stroke (<24 hours; OXVASC [Oxford Vascular Study]). Isolated EV fractions were subjected to untargeted proteomic analysis by liquid chromatography mass-spectrometry/mass-spectrometry and then applied to macrophages in culture to investigate inflammatory gene expression...
May 23, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28523230/targeting-resolution-of-neuroinflammation-after-ischemic-stroke-with-a-lipoxin-a4-analog-protective-mechanisms-and-long-term-effects-on-neurological-recovery
#9
Kimberly E Hawkins, Kelly M DeMars, Jon C Alexander, Lauren G de Leon, Sean C Pacheco, Christina Graves, Changjun Yang, Austin O McCrea, Jan C Frankowski, Timothy J Garrett, Marcelo Febo, Eduardo Candelario-Jalil
BACKGROUND: Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti-inflammatory, pro-resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML-111. We hypothesized that post-ischemic, intravenous treatment with BML-111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats...
May 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28517732/t-cells-and-macrophages-peak-weeks-after-experimental-stroke-spatial-and-temporal-characteristics
#10
Nina Vindegaard, Clara Muñoz-Briones, Henrik H El Ali, Lotte Kellemann Kristensen, Rune Skovgaard Rasmussen, Flemming Fryd Johansen, Henrik Hasseldam
The activities of the central and peripheral immune systems impact neurological outcome after ischemic stroke. However, studies investigating the temporal profile of leukocyte infiltration, especially T-cell recruitment, are sparse. Our aim was to investigate leukocyte infiltration at different time points after experimental stroke in mice. Permanent middle cerebral artery occlusion was performed on 11 weeks old C57BL/6J mice, allowed to survive for 1, 3, 8, 14 or 28 days. In addition to infarct size measurements, detailed immunohistochemical analyses of T-cell and macrophage influx were performed...
May 18, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28487994/cd74-immunoreactive-activated-m1-microglia-are-shown-late-in-the-gerbil-hippocampal-ca1-region-following-transient-cerebral-ischemia
#11
In Koo Hwang, Joon Ha Park, Tae-Kyeong Lee, Dae Won Kim, Ki-Yeon Yoo, Ji Hyeon Ahn, Yang Hee Kim, Jun Hwi Cho, Young-Myeong Kim, Moo-Ho Won, Seung Myung Moon
Activated M1 microglia secrete proinflammatory cytokines into damaged brain areas. The present study examined activated M1 microglial morphology and expression in the hippocampal Cornu Ammonis (CA) 1 region, which is vulnerable to transient ischemia. Transient cerebral ischemia was performed for 5 min in gerbils, and neuronal death in the CA1 region following transient cerebral ischemia was confirmed using cresyl violet staining, neuronal nuclear antigen immunohistochemistry and Fluoro‑Jade B histofluorescent staining...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28482260/increased-expression-of-tfpi-in-human-carotid-stenosis
#12
Benedicte Stavik, Sverre Holm, Sandra Espada, Nina Iversen, Bjørnar Sporsheim, Vigdis Bjerkeli, Tuva Børresdatter Dahl, Per Morten Sandset, Mona Skjelland, Terje Espevik, Grethe Skretting, Bente Halvorsen
INTRODUCTION: Tissue factor (TF) pathway inhibitor (TFPI) is the physiological inhibitor of TF induced blood coagulation and two isoforms exists, TFPIα and TFPIβ. In atherosclerotic plaques, TFPI may inhibit TF activity and thrombus formation, which is the main cause of ischemic stroke in carotid artery disease. We aimed to identify the isoforms of TFPI present in human carotid plaques and potential sources of TFPI. MATERIALS AND METHODS: Human atherosclerotic plaques from carotid endarterectomies were used for mRNA and immunohistochemistry analyses...
April 28, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28471481/cytotoxic-lymphocytes-and-atherosclerosis-significance-mechanisms-and-therapeutic-challenges
#13
Tin Kyaw, Karlheinz Peter, Li Yi, Peter Tipping, Ban-Hock Toh, Alex Bobik
Cytotoxic lymphocytes encompass natural killer (NK) lymphocytes (cells) and cytotoxic T cells that include CD8+ T cells, NKT cells, gamma, delta (γδ)-T cells and human CD4 + CD28- T cells. These cells play critical roles in inflammatory diseases and in controlling cancers and infections. Cytotoxic lymphocytes can be activated via a number of mechanisms that may involve dendritic cells, macrophages, cytokines or surface proteins on stressed cells. Upon activation, they secrete proinflammatory cytokines as well as anti-inflammatory cytokines, chemokines and cytotoxins to promote inflammation and development of atherosclerotic lesions including vulnerable lesions, which are strongly implicated in myocardial infarctions and strokes...
May 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28413029/evidence-for-the-involvement-of-matrix-degrading-metalloproteinases-mmps-in-atherosclerosis
#14
Bethan A Brown, Helen Williams, Sarah J George
Atherosclerosis leads to blockage of arteries, culminating in myocardial infarction, and stroke. The involvement of matrix-degrading metalloproteinases (MMPs) in atherosclerosis is established and many studies have highlighted the importance of various MMPs in this process. MMPs were first implicated in atherosclerosis due to their ability to degrade extracellular matrix components, which can lead to increased plaque instability. However, more recent work has highlighted a multitude of roles for MMPs in addition to breakdown of extracellular matrix proteins...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28392564/the-immunology-of-atherosclerosis
#15
REVIEW
Anton Gisterå, Göran K Hansson
Cardiovascular disease is the leading cause of death worldwide, both in the general population and among patients with chronic kidney disease (CKD). In most cases, the underlying cause of the cardiovascular event is atherosclerosis - a chronic inflammatory disease. CKD accelerates atherosclerosis via augmentation of inflammation, perturbation of lipid metabolism, and other mechanisms. In the artery wall, subendothelial retention of plasma lipoproteins triggers monocyte-derived macrophages and T helper type 1 (TH1) cells to form atherosclerotic plaques...
June 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28389473/st2-il-33-dependent-microglial-response-limits-acute-ischemic-brain-injury
#16
Yuanyuan Yang, Huan Liu, Haiyue Zhang, Qing Ye, Jianyi Wang, Boyu Yang, Leilei Mao, Wen Zhu, Rehana K Leak, Bo Xiao, Binfeng Lu, Jun Chen, Xiaoming Hu
ST2, a member of the interleukin (IL) 1 receptor family, and its ligand IL-33 play critical roles in immune regulation and inflammatory responses. This study explores the roles of endogenous IL-33/ST2 signaling in ischemic brain injury and elucidates the underlying mechanisms of action. The expression of IL-33 rapidly increased in oligodendrocytes and astrocytes after 60 min transient middle cerebral artery occlusion (tMCAO). ST2 receptor deficiency exacerbated brain infarction 3 d after tMCAO as well as distal permanent MCAO...
May 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28385306/detection-of-atherosclerotic-inflammation-by-68-ga-dotatate-pet-compared-to-18-f-fdg-pet-imaging
#17
Jason M Tarkin, Francis R Joshi, Nicholas R Evans, Mohammed M Chowdhury, Nichola L Figg, Aarti V Shah, Lakshi T Starks, Abel Martin-Garrido, Roido Manavaki, Emma Yu, Rhoda E Kuc, Luigi Grassi, Roman Kreuzhuber, Myrto A Kostadima, Mattia Frontini, Peter J Kirkpatrick, Patrick A Coughlin, Deepa Gopalan, Tim D Fryer, John R Buscombe, Ashley M Groves, Willem H Ouwehand, Martin R Bennett, Elizabeth A Warburton, Anthony P Davenport, James H F Rudd
BACKGROUND: Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET), [(18)F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. OBJECTIVES: This study tested the efficacy of gallium-68-labeled DOTATATE ((68)Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation...
April 11, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#18
Amy E Baek, Nadia R Sutton, Danica Petrovic-Djergovic, Hui Liao, Jessica Ray, Joan Park, Yogendra Kanthi, David J Pinsky
Background -Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic (TG) mouse expressing human CD39 (hCD39)...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28366792/serum-macrophage-migration-inhibitory-factor-concentrations-correlate-with-prognosis-of-traumatic-brain-injury
#19
Ding-Bo Yang, Wen-Hua Yu, Xiao-Qiao Dong, Zu-Yong Zhang, Quan Du, Qiang Zhu, Zhi-Hao Che, Hao Wang, Yong-Feng Shen, Li Jiang
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a well-known pro-inflammatory cytokine. Serum MIF concentrations are associated with the severity and prognosis of ischemic stroke. METHODS: In this prospective, observational study, white blood cell (WBC) count and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and MIF among 108 severe traumatic brain injury (TBI) patients and 108 controls were measured...
March 30, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28323006/the-role-of-sumoylation-in-cerebral-hypoxia-and-ischemia
#20
REVIEW
Myriam Peters, Betty Wielsch, Johannes Boltze
The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous processes in eukaryotic cells. SUMOylation also represents a key response and adaption mechanism to different forms of metabolic stress. The central nervous system (CNS) and neurons in particular are highly susceptible to hypoxic-ischemic stress due to the lack of significant oxygen and energy reserves. SUMOylation is observed in many molecular responses to metabolic stress in the brain, and is therefore supposed to represent an endogenous neuroprotective mechanism...
July 2017: Neurochemistry International
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