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Coagulation pathways

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https://www.readbyqxmd.com/read/27925197/factor-xa-signaling-contributes-to-the-pathogenesis-of-inflammatory-diseases
#1
REVIEW
Safieh Ebrahimi, Sara Rezaei, Parvaneh Seiri, Mikhail Ryzhikov, Seyed Issac Hashemy, Seyed Mahdi Hassanian
The coagulation protease Factor Xa (FXa) triggers a variety of signaling pathways through activation of protease-activated receptors (PARs) and non-PAR receptors. FXa-mediated signaling is strongly implicated in the pathogenesis of several inflammatory diseases including fibrosis, cardiovascular diseases and cancer. Thus, targeting of FXa can have great clinical significance in terms of the treatment of these disorders. This review summarizes the current knowledge about the mechanism of FXa signaling in cellular and animal systems under (patho)physiological conditions for a better understanding and hence a better management of FXa-induced disorders...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27922857/comprehensive-assessment-of-the-arginine-pathway-and-its-relationship-to-inflammation-in-hiv
#2
Sahera Dirajlal-Fargo, S M Khurshid Alam, Abdus Sattar, Manjusha Kulkarni, Nicholas Funderburg, W H Wilson Tang, Grace A Mccomsey
BACKGROUND: Nitric oxide helps maintain vascular function and is generated through the oxidation of arginine. Whether altered arginine metabolism may lead to elevated levels of inflammation in HIV is unclear. METHODS: We performed a cross-sectional analysis of HIV-infected adults on stable ART with HIV-1 RNA < 50 copies/mL and HIV-uninfected controls. We measured biomarkers in the arginine pathway, markers of systemic inflammation, and monocyte activation. T-tests, chi-square tests and propensity score matching analyses were used to compare markers by HIV status, and multiple linear regressions were used to assess associations of arginine metabolites with markers of inflammation...
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27919911/in-vitro-activation-of-coagulation-by-human-neutrophil-dna-and-histone-proteins-but-not-neutrophil-extracellular-traps
#3
Denis F Noubouossie, Matthew F Whelihan, Yuan-Bin Yu, Erica Sparkenbaugh, Rafal Pawlinski, Dougald M Monroe, Nigel S Key
NETosis is a physiological process in which neutrophils release their nuclear material in the form of neutrophil extracellular traps (NETs). NETs have been reported to directly promote thrombosis in animal models. Although the effects of purified NET components including DNA, histone proteins and neutrophil enzymes on coagulation have been characterized, the mechanism by which intact NETs promote thrombosis is largely unknown. In this study, human neutrophils were stimulated to produce NETs in platelet-free plasma (PFP) or in buffer using PMA or calcium ionophore...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27913856/direct-oral-anticoagulants-an-overview-for-the-interventional-radiologist
#4
Pradesh Kumar, Rajeev Ravi, Gaurav Sundar, Caroline Shiach
The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing...
December 2, 2016: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/27913544/treatment-of-rare-factor-deficiencies-in-2016
#5
Flora Peyvandi, Marzia Menegatti
Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K-dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913422/factor-xi-deficiency-enhances-the-pulmonary-allergic-response-to-house-dust-mite-in-mice-independent-of-factor-xii
#6
Ingrid Stroo, Jack Yang, Johannes Daan de Boer, Joris J T H Roelofs, Cornelis van 't Veer, Francis J Castellino, Sacha Zeerleder, Tom van der Poll
Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system, and its possible route of activation, in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO) and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27910925/thrombomodulin-regulates-monocye-differentiation-via-pkc%C3%AE-and-erk1-2-pathway-in-vitro-and-in-atherosclerotic-artery
#7
Chien-Sung Tsai, Yi-Wen Lin, Chun-Yao Huang, Chun-Min Shih, Yi-Ting Tsai, Nai-Wen Tsao, Chin-Sheng Lin, Chun-Che Shih, Hellen Jeng, Feng-Yen Lin
Thrombomodulin (TM) modulates the activation of protein C and coagulation. Additionally, TM regulates monocyte migration and inflammation. However, its role on monocyte differentiation is still unknown. We investigated the effects of TM on monocyte differentiation. First, we found that TM was increased when THP-1 cells were treated with phorbol-12-myristate-13-acetate (PMA). Overexpression of TM enhanced the macrophage markers, CD14 and CD68 expression in PMA-induced THP-1. TM siRNA depressed the PMA-induced increase of p21(Cip1/WAF1) via ERK1/2-NF-kB p65 signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902465/gene-and-microrna-modulation-upon-trabectedin-treatment-in-a-human-intrahepatic-cholangiocarcinoma-paired-patient-derived-xenograft-and-cell-line
#8
Caterina Peraldo Neia, Giuliana Cavalloni, Giovanna Chiorino, Paola Ostano, Massimo Aglietta, Francesco Leone
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. Trabectedin has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of trabectedin at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of trabectedin were explored in the in vitro model. In vitro, trabectedin inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899993/predictive-value-of-microparticle-associated-tissue-factor-activity-for-permeability-glycoprotein-mediated-multidrug-resistance-in-cancer
#9
Antonio Angelini, Sebastiano Miscia, Maria Antonietta Centurione, Roberta Di Pietro, Lucia Centurione
Multidrug resistance (MDR) protein 1, which is also known as permeability glycoprotein (Pgp), and tissue factor (TF) are recurrently overexpressed on the surface of cancer cells, likely in response to stimuli such as chemotherapy. Microparticles (MPs) released from cancer cells into the bloodstream express tumour markers on their surface that may be useful as predictive biomarkers for evaluating disease progression. The present study measured the level of TF/factor VII (FVII)-dependent coagulation of MPs isolated from the plasma of cancer patients with various tumours, who were undergoing chemotherapy...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27892526/comprehensive-gene-expression-meta-analysis-and-integrated-bioinformatic-approaches-reveal-shared-signatures-between-thrombosis-and-myeloproliferative-disorders
#10
Prabhash Kumar Jha, Aatira Vijay, Anita Sahu, Mohammad Zahid Ashraf
Thrombosis is a leading cause of morbidity and mortality in patients with myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Despite the attempts to establish a link between them, the shared biological mechanisms are yet to be characterized. An integrated gene expression meta-analysis of five independent publicly available microarray data of the three diseases was conducted to identify shared gene expression signatures and overlapping biological processes...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27886814/regulation-of-platelet-activation-and-coagulation-and-its-role-in-vascular-injury-and-arterial-thrombosis
#11
REVIEW
Maurizio Tomaiuolo, Lawrence F Brass, Timothy J Stalker
Hemostasis requires tightly regulated interaction of the coagulation system, platelets, blood cells, and vessel wall components at a site of vascular injury. Dysregulation of this response may result in excessive bleeding if the response is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia if the response is robust. Studies have elucidated the major molecular signaling pathways responsible for platelet activation and aggregation. Antithrombotic agents targeting these pathways are in clinical use...
January 2017: Interventional cardiology clinics
https://www.readbyqxmd.com/read/27886531/coagulation-and-sepsis
#12
REVIEW
Marcel Levi, Tom van der Poll
Severe sepsis is almost invariably associated with systemic activation of coagulation. There is ample evidence that demonstrates a wide-ranging cross-talk between hemostasis and inflammation, which is probably implicated in the pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only leads to initiation and propagation of coagulation activity, but coagulation also markedly influences inflammation. Molecular mechanisms that play a role in inflammation-induced effects on coagulation have been recognized in much detail...
November 19, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27878206/new-findings-on-venous-thrombogenesis
#13
James R Byrnes, Alisa S Wolberg
Venous thrombosis (VT) is the third most common cause of cardiovascular death worldwide. Complications from VT and pulmonary embolism are the leading cause of lost disability-adjusted life years. Risks include genetic (e.g., non-O blood group, activated protein C resistance, hyperprothrombinemia) and acquired (e.g., age, surgery, cancer, pregnancy, immobilisation, female hormone use) factors. Pathophysiologic mechanisms that promote VT are incompletely understood, but involve abnormalities in blood coagulability, vessel function, and flow (so-called Virchow's Triad)...
November 23, 2016: Hämostaseologie
https://www.readbyqxmd.com/read/27868334/consensus-on-the-standardization-of-terminology-in-thrombotic-thrombocytopenic-purpura-and-related-thrombotic-microangiopathies
#14
M Scully, S Cataland, P Coppo, J de la Rubia, K D Friedman, J Kremer Hovinga, B Lämmle, M Matsumoto, K Pavenski, E Sadler, R Sarode, H Wu
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic Microangiopathy is a broad pathophysiological process that leads to microangiopathic hemolytic anemia, thrombocytopenia and involves capillary and small vessel platelet aggregates. The most common cause being disseminated intravascular coagulation (DIC), which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia (MAHAT), including cancer, infection, transplantation, drugs, autoimmune disease and pre-eclampsia and HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome in pregnancy...
November 21, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27866916/blood-coagulation-in-immunothrombosis-at-the-frontline-of-intravascular-immunity
#15
REVIEW
Florian Gaertner, Steffen Massberg
While hemostasis is the physiological process that prevents blood loss after vessel injury, thrombosis is often portrayed as a pathologic event involving blood coagulation and platelet aggregation eventually leading to vascular occlusion and tissue damage. However, recent work suggests that thrombosis can also be a physiological process, termed immunothrombosis, initiated by the innate immune system providing a first line of defense to locally control infection. Fibrin forms the structural basis of immunothrombotic clots and its assembly involves the concerted action of coagulation factors, platelets and leukocytes...
November 17, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27864149/mechanistic-insight-into-the-procoagulant-activity-of-tumor-derived-apoptotic-vesicles
#16
Morad-Rémy Muhsin-Sharafaldine, Bailey R Kennedy, Sarah C Saunderson, Catrin R Buchanan, Amy C Dunn, James M Faed, Alexander D McLellan
BACKGROUND: Chemotherapy induces the release of apoptotic vesicles (ApoV) from the tumor plasma membrane. Tumor ApoV may enhance the risk of thrombotic events in cancer patients undergoing chemotherapy. However, the relative contribution of ApoV to coagulation and the pathways involved remain poorly characterized. In addition, this study sets out to compare the procoagulant activity of chemotherapy-induced ApoV with their cell of origin and to determine the mechanisms of ApoV-induced coagulation...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27862752/improving-the-binding-affinity-of-in-vitro-evolved-cyclic-peptides-by-inserting-atoms-into-the-macrocycle-backbone
#17
Jonas Wilbs, Simon J Middendorp, Christian Heinis
Cyclic peptides binding to targets of interest can be generated efficiently with powerful in vitro display techniques, such as phage display or mRNA display. The cyclic peptide libraries screened with these methods are generated by altering in a combinatorial fashion the amino acid sequence of the peptides, the number of amino acids in the macrocycle rings, and the cyclization chemistry. A structural element that cannot easily be varied in the cyclic peptides is the backbone, which is built from amino acids, each of which contributes three atoms to the macrocyclic ring structure...
November 11, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27858977/atypical-presentation-of-livedo-racemosa-in-a-factor-v-leiden-heterozygous-positive-patient-with-pseudomonas-aeruginosa-urosepsis
#18
Jesse Johnston, Rowland Noakes, Kurt Davidson
Impairment of the protein C pathway, detectable by reduced plasma levels of activated protein C (APC), are risk factors for venous thrombosis. Activated protein C maintains clotting homeostasis by regulation of pro-coagulant factors Va and VIIIa. Both infection and the factor V Leiden mutation reduce the formation of APC from protein C in the blood. With low levels of APC, excess factors Va and VIIIa exist, increasing the risk of thrombus formation. Livedo racemosa is characterised by a striking, violaceous branch-like pattering of the skin...
November 12, 2016: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/27858671/effect-of-circulating-tissue-factor-on-hypercoagulability-in-type-2-diabetes-mellitus%C3%A2-studied-by-rheometry-and-dielectric%C3%A2-blood-coagulometry
#19
Isao Uchimura, Makoto Kaibara, Masayuki Nagasawa, Yoshihito Hayashi
BACKGROUND: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. OBJECTIVE: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). METHODS: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. RESULTS: The average coagulation time was significantly shorter for T2DM patients than for healthy controls...
November 16, 2016: Biorheology
https://www.readbyqxmd.com/read/27855271/experimental-lung-injury-reduces-klf2-to-increase-endothelial-permeability-via-regulation-of-rapgef3-rac1-signaling
#20
Ru-Ting Huang, David Wu, Angelo Meliton, Myung-Jin Oh, Matthew Krause, Joyce A Lloyd, Recep Nigdelioglu, Robert B Hamanaka, Mukesh K Jain, Anna Birukova, John P Kress, Konstantin G Birukov, Gökhan M Mutlu, Yun Fang
RATIONALE: The acute respiratory distress syndrome (ARDS) is caused by widespread endothelial barrier disruption and uncontrolled cytokine storm. Genome-wide association studies (GWAS) have linked multiple genes to ARDS. Although mechano-sensitive transcription factor Krüppel-like factor 2 (KLF2) is a major regulator of endothelial function, its role in regulating pulmonary vascular integrity in lung injury and ARDS-associated GWAS genes remains poorly understood. OBJECTIVES: To examine KLF2 expression in multiple animal models of acute lung injury and further elucidate the KLF2-mediated pathways involved in endothelial barrier disruption and cytokine storm in experimental lung injury...
November 17, 2016: American Journal of Respiratory and Critical Care Medicine
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