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https://www.readbyqxmd.com/read/29332224/phosphatidylserine-exposing-blood-and-endothelial-cells-contribute-to-the-hypercoagulable-state-in-essential-thrombocythemia-patients
#1
Dongxia Tong, Muxin Yu, Li Guo, Tao Li, Jihe Li, Valerie A Novakovic, Zengxiang Dong, Ye Tian, Junjie Kou, Yayan Bi, Jinghua Wang, Jin Zhou, Jialan Shi
The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P < 0...
January 13, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29331583/importins-%C3%AE-and-%C3%AE-signaling-mediates-endothelial-cell-inflammation-and-barrier-disruption
#2
Antony Leonard, Arshad Rahman, Fabeha Fazal
Nucleocytoplasmic shuttling via importins is central to the function of eukaryotic cells and an integral part of the processes that lead to many human diseases. In this study, we addressed the role of α and β importins in the mechanism of endothelial cell (EC) inflammation and permeability, important pathogenic features of many inflammatory diseases such as acute lung injury and atherosclerosis. RNAi-mediated knockdown of importin α4 or α3 each inhibited NF-κB activation, proinflammatory gene (ICAM-1, VCAM-1, and IL-6) expression, and thereby endothelial adhesivity towards HL-60 cells, upon thrombin challenge...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29324883/masp-1-of-the-complement-system-enhances-clot-formation-in-a-microvascular-whole-blood-flow-model
#3
Lorenz Jenny, József Dobó, Péter Gál, Gábor Pál, Wilbur A Lam, Verena Schroeder
The complement and coagulation systems closely interact with each other. These interactions are believed to contribute to the proinflammatory and prothrombotic environment involved in the development of thrombotic complications in many diseases. Complement MASP-1 (mannan-binding lectin-associated serine protease-1) activates coagulation factors and promotes clot formation. However, this was mainly shown in purified or plasma-based static systems. Here we describe the role of MASP-1 and complement activation in fibrin clot formation in a microvascular, whole blood flow model...
2018: PloS One
https://www.readbyqxmd.com/read/29323190/angiopoietins-bind-thrombomodulin-and-inhibit-its-function-as-a-thrombin-cofactor
#4
Christopher Daly, Xiaozhong Qian, Carla Castanaro, Elizabeth Pasnikowski, Xiabo Jiang, Benjamin R Thomson, Susan E Quaggin, Nicholas Papadopoulos, Yang Wei, John S Rudge, Gavin Thurston, George D Yancopoulos, Samuel Davis
Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2) are ligands for Tie2, an endothelial-specific receptor tyrosine kinase that is an essential regulator of angiogenesis. Here we report the identification, via expression cloning, of thrombomodulin (TM) as another receptor for Ang1 and Ang2. Thrombomodulin is an endothelial cell surface molecule that plays an essential role as a coagulation inhibitor via its function as a cofactor in the thrombin-mediated activation of protein C, an anticoagulant protein, as well as thrombin-activatable fibrinolysis inhibitor (TAFI)...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29305843/circulating-microparticles-levels-are-increased-in-patients-with-diabetic-kidney-disease-a-case-control-research
#5
Kathryna Fontana Rodrigues, Nathalia Teixeira Pietrani, Ana Paula Fernandes, Adriana Aparecida Bosco, Maira Cândida Rodrigues de Sousa, Ieda de Fátima Oliveira Silva, Josianne Nicácio Silveira, Fernanda Magalhães Freire Campos, Karina Braga Gomes
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with chronic lowgrade inflammation. Microparticles (MPs) are extracellular microvesicles released during apoptosis and cellular activation. The MP's pro-coagulant and pro-inflammatory activities are involved in endothelial dysfunction observed in T2DM patients. This study aimed to evaluate the circulating MPs profile in T2DM patients with diabetic kidney disease (DKD) and correlate it with clinical and laboratorial parameters. METHODS: MPs derived from platelets (PMPs), leukocytes (LMPs), endothelial cells (EMPs), and expressing tissue factor (TFMPs) were measured by flow cytometry, in plasma of 39 DKD patients and 30 non-diabetic controls...
January 3, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29296958/characterizing-the-o-glycosylation-landscape-of-human-plasma-platelets-and-endothelial-cells
#6
Sarah L King, Hiren J Joshi, Katrine T Schjoldager, Adnan Halim, Thomas D Madsen, Morten H Dziegiel, Anders Woetmann, Sergey Y Vakhrushev, Hans H Wandall
The hemostatic system comprises platelet aggregation, coagulation, and fibrinolysis, and is critical to the maintenance of vascular integrity. Multiple studies indicate that glycans play important roles in the hemostatic system; however, most investigations have focused on N-glycans because of the complexity of O-glycan analysis. Here we performed the first systematic analysis of native-O-glycosylation using lectin affinity chromatography coupled to liquid chromatography mass spectrometry (LC-MS)/MS to determine the precise location of O-glycans in human plasma, platelets, and endothelial cells, which coordinately regulate hemostasis...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296764/antiangiogenic-effects-of-decorin-restored-by-unfractionated-low-molecular-weight-and-nonanticoagulant-heparins
#7
Amy K L Chui, Tilini N Gunatillake, Vera Ignjatovic, Paul T Monagle, Padma Murthi, Shaun P Brennecke, John M Whitelock, Joanne M Said
Pregnancies affected by preeclampsia (PE) or fetal growth restriction (FGR) display increases in thrombin generation and reductions in angiogenesis and cell growth. There is significant interest in the potential for low molecular weight heparins (LMWHs) to reduce the recurrence of PE and FGR. However, LMWH is associated with an increased risk of bleeding. Therefore, it is of vital importance to determine the exact molecular function of heparins in pregnancy if they are used as therapy for pregnant women. We aimed to determine this using our model for PE/FGR in microvascular endothelial cells...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285085/unfractionated-heparin-protects-the-protein-c-system-against-lipopolysaccharide-induced-damage-in-vivo-and-in-vitro
#8
Dongmei Zhao, Renyu Ding, Yina Liu, Xiaohan Yin, Zhidan Zhang, Xiaochun Ma
Activation of protein C is greatly enhanced by the presence of thrombomodulin (TM) and endothelial protein C receptor (EPCR) on the endothelial surface. Impairment of the anticoagulant protein C system occurs during endotoxemia and contributes to sepsis-associated hypercoagulability. Previous studies have demonstrated that unfractionated heparin (UFH) can attenuate coagulation in endotoxemic mice. However, whether UFH has an effect on the protein C system remains to be elucidated. The current study evaluated the therapeutic effect of UFH on the protein C system in a mouse model of lipopolysaccharide (LPS)-induced sepsis, and further investigated the effect of UFH on the expression of TM and EPCR in vitro using human umbilical vein endothelial cells (HUVECs)...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29258201/impact-of-unsaturated-fatty-acids-on-cytokine-driven-endothelial-cell-dysfunction
#9
Simon Trommer, Anja Leimert, Michael Bucher, Julia Schumann
Polyunsaturated fatty acids (PUFA) are reported to exert prophylactic and acute therapeutic effects in diseases linked to endothelial dysfunction. In the present study, the consequences of a PUFA enrichment of endothelial cells (cell line TIME) on cell viability, expression of the cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1), synthesis of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1), and production of the coagulation factors plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and tissue factor (TF) was analyzed in parallel...
December 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29242228/bmscs-ameliorate-septic-coagulopathy-through-suppressing-inflammation-in-cecal-ligation-and-puncture-induced-sepsis
#10
Shunyao Xu, Zhen Zhou, Hao Li, Ziying Liu, Xiaojun Pan, Fen Wang, Yueyue Huang, Xiaogang Li, Yunbei Xiao, Jingye Pan, Cong Wang, Dequan Li
Sepsis is an aggressive and life-threatening systemic inflammatory response with a high mortality. Inflammation and coagulation play crucial roles in the pathogenesis of sepsis in a mutually promoting manner. Unlike other single-target molecular therapies that have no obvious effects on clinical sepsis, the bone marrow stromal cell (BMSC) therapy offers a broader spectrum of activities ranging from immune and inflammation suppression to tissue regeneration. In this report, we demonstrated that BMSC injection attenuated the septic coagulopathy...
December 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29240916/study-on-the-anti-endotoxin-effect-of-sinomenine-using-an-agilent-genome-array
#11
Yiyi Hu, Bin Li, Libin Wen, Kongwang He
Background: Endotoxin is a significant contributing factor underlying the occurrence of fever, diarrhea, inflammation, edema, coagulation, shock, and other syndromes associated with Gram-negative bacterial infections. To date, there is no effective treatment for endotoxemia. Aim: The aim of this study was to characterize differentially expressed genes in sinomenine-treated and LPS-induced endothelial cells by microarray analysis, and to determine the potential pharmacological activity of sinomenine...
December 12, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/29231707/sulfonate-groups-and-saccharides-as-essential-structural-elements-in-heparin-mimicking-polymers-used-as-surface-modifiers-optimization-of-relative-contents-for-anti-thrombogenic-properties
#12
Xianshuang Chen, Hao Gu, Zhonglin Lyu, Xiaoli Liu, Lei Wang, Hong Chen, John Law Brash
Blood compatibility is a long sought-after goal in biomaterials research, but remains an elusive one, and in spite of extensive work in this area, there is still no definitive information on the relationship between material properties and blood responses such as coagulation and thrombus formation. Materials modified with heparin-mimicking polymers (HMP) have shown promise, and indeed may be seen as comparable to materials modified with heparin itself. In this work, heparin was conceptualized as consisting of two major structural elements: saccharide-containing and sulfonate-containing units, and polymers based on this concept were developed...
December 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29228619/fibrin-bearing-microparticles-marker-of-thrombo-embolic-events-in-pancreatic-and-colorectal-cancers
#13
Diane Mege, Lydie Crescence, Mehdi Ouaissi, Igor Sielezneff, Regis Guieu, Françoise Dignat-George, Christophe Dubois, Laurence Panicot-Dubois
Background: Microparticles (MPs) are plasma membrane-derived extracellular vesicles present in the bloodstream. We have described a specific signature of MPs, called microparticulosome, in colorectal (CRC) and pancreatic (PC) cancers. We observed that levels of fibrin-bearing MPs were significantly increased in patients suffering from PC and CRC in comparison with control groups. Here, we hypothesised that fibrin-MPs may constitute a relevant biomarker of thrombosis associated with cancer...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215061/local-production-of-activated-factor-x-in-atherosclerotic-plaque-induced-vascular-smooth-muscle-cell-senescence
#14
Fumihiro Sanada, Jun Muratsu, Rei Otsu, Hideo Shimizu, Nobutaka Koibuchi, Kazutaka Uchida, Yoshiaki Taniyama, Shinichi Yoshimura, Hiromi Rakugi, Ryuichi Morishita
Our previous study demonstrated that coagulation factor Xa (FXa) induced endothelial cell senescence, resulting in inflammation and impaired angiogenesis. This mechanism is dictated through protease-activated receptors, PARs, insulin-like growth factor-binding protein 5 (IGFBP-5), and p53. Activation of PARs contributes to the pathophysiology of several chronic inflammatory diseases, including atherosclerosis. Thus, we speculated that similar mechanism might participate in the progression of atherosclerotic plaques...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207649/sulodexide-recovers-endothelial-function-through-reconstructing-glycocalyx-in-the-balloon-injury-rat-carotid-artery-model
#15
Tianjia Li, Xinnong Liu, Zhewei Zhao, Leng Ni, Changwei Liu
Disruption of endothelial cell function is a principle event in cardiovascular disease. Accordingly, therapies have mostly focused on repairing the endothelium, but little attention has been paid to the reconstruction of glycocalyx, which covers the endothelium and protects the function of endothelial cells. Sulodexide has a similar glycosaminoglycan structure to glycocalyx, so it is assumed to be effective in remodeling the glycocalyx following damage. We assessed the effect of sulodexide on glycocalyx remodeling and endothelial function in the balloon-injury rat carotid artery model...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29197958/immunohaemostasis-a-new-view-on-haemostasis-during-sepsis
#16
REVIEW
Xavier Delabranche, Julie Helms, Ferhat Meziani
Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now recognised, and thrombin has become a partner for survival, while it was seen only as one of the "principal suspects" of multiple organ failure and death during septic shock. This review is first focused on pathophysiology. The role of contact activation system, polyphosphates and neutrophil extracellular traps has emerged, offering new potential therapeutic targets...
December 2, 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/29195855/modeling-of-the-effects-of-il-17-and-tnf-%C3%AE-on-endothelial-cells-and-thrombus-growth
#17
Anass Bouchnita, Pierre Miossec, Alen Tosenberger, Vitaly Volpert
Rheumatoid and psoriatic arthritis are chronic inflammatory diseases, with massive increase of cardiovascular events (CVE), and contribution of the cytokines TNF-α and IL-17. Chronic inflammation inside the joint membrane or synovium results from the activation of fibroblasts/synoviocytes, and leads to the release of cytokines from monocytes (Tumor Necrosis Factor or TNF) and from T lymphocytes (Interleukin-17 or IL-17). At the systemic level, the very same cytokines affect endothelial cells and vessel wall...
November 28, 2017: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/29193703/inflammation-and-thrombosis-roles-of-neutrophils-platelets-and-endothelial-cells-and-their-interactions-in-thrombus-formation-during-sepsis
#18
REVIEW
Toshiaki Iba, Jerrold H Levy
The inflammatory response and the activation of coagulation are two important responses in a host's defense against infection. These mechanisms do not work independently but cooperate in a complex and synchronous manner. Recent research has also shed light on the critical role of thrombus formation that prevents the dissemination of microbes. The cellular components of blood vessels, leukocytes, platelets, erythrocytes, and vascular endothelial cells play significant roles in the development of thrombi in combination with activation of the coagulation system...
November 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29178990/variants-in-chondroitin-sulfate-metabolism-genes-in-thrombotic-storm
#19
Karen Nuytemans, Thomas L Ortel, Lissette Gomez, Natalia Hofmann, Natalie Alves, Nicole Dueker, Ashley Beecham, Patrice Whitehead, Susan Hahn Estabrooks, Craig S Kitchens, Doruk Erkan, Leonardo R Brandão, Andra H James, Roshni Kulkarni, Marilyn J Manco-Johnson, Margaret A Pericak-Vance, Jeffery M Vance
INTRODUCTION: Thrombotic storm (TS) presents as a severe, acute thrombotic phenotype, characterized by multiple clotting events and frequently affecting younger adults. Understanding the extensive hypercoagulation of an extreme phenotype as TS will also provide insight into the pathogenesis of a wider spectrum of thrombotic disorders. MATERIAL AND METHODS: We completed whole exome sequencing on 26 TS patients, including 1 multiplex family, 13 trios and 12 isolated TS patients...
November 21, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29126301/coagulation-testing-in-the-core-laboratory
#20
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
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