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Coagulation pathways

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https://www.readbyqxmd.com/read/28089408/the-various-assays-for-measuring-activity-states-of-factor-viia-in-plasma-and-therapeutic-products-diagnostic-value-and-analytical-usefulness-in-various-pathophysiological-states
#1
REVIEW
Jean Amiral, Claire Dunois, Cédric Amiral, Jerard Seghatchian
The key coagulation factor FVII, and its activated form FVIIa, present a major interest for their role at the initiation phase of blood coagulation, and because they can activate all blood coagulation cascade, through the extrinsic, but also the intrinsic pathway. Blood activation initiated through FVII is first presented, as it is understood nowadays. Measurement of FVII and FVIIa were of main interest for epidemiological studies, but FVIIa contribution to assay results was only deduced. The introduction of specific FVIIa assays, functional or immunoassays, allowed measuring directly FVIIa without any interference of non-activated FVII, or other coagulation factors or their activated forms...
December 29, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28088517/osborne-mendel-rats-simultaneously-develop-cardiac-and-renal-dysfunction-left-atrial-thrombosis-peripheral-artery-occlusion-and-ascending-aortic-dissection
#2
Makoto Asahina, Hideki Matsumoto, Yoshitaka Yasuhara, Noriko Suzuki, Ritsuko Takami, Michiyasu Takeyama, Ryuichi Tozawa
Although chronic kidney disease (CKD) is strongly associated with onsets of cardiovascular disease (CVD), the pathogenic mechanism between these diseases has not been fully understood. To develop and validate new therapeutic strategies for this complication, appropriate experimental models that reflect the complexity of the underlying pathophysiology are needed. The Osborne-Mendel (OM) rat was identified as an atherosclerosis-prone and a premature-death rat strain among 16 inbred rat strains when fed high-cholesterol containing diet...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28081568/non-lethal-endotoxin-injection-a-rat-model-of-hypercoagulability
#3
Marjory B Brooks, James R Turk, Abraham Guerrero, Padma K Narayanan, John P Nolan, Elizabeth G Besteman, Dennis W Wilson, Roberta A Thomas, Cindy E Fishman, Karol L Thompson, Heidrun Ellinger-Ziegelbauer, Jennifer B Pierson, April Paulman, Alan Y Chiang, Albert E Schultze
Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response...
2017: PloS One
https://www.readbyqxmd.com/read/28079606/relationship-between-alternative-resuscitation-strategies-host-response-and-injury-biomarkers-and-outcome-in-septic-shock-analysis-of-the-protocol-based-care-for-early-septic-shock-study
#4
John A Kellum, Francis Pike, Donald M Yealy, David T Huang, Nathan I Shapiro, Derek C Angus
OBJECTIVES: The Protocol-based Care for Early Septic Shock trial found no differences across alternative resuscitation strategies in all-cause mortality. A separate aim was to determine whether differences in resuscitation strategies affected trajectories of biomarkers of key pathways associated with downstream clinical outcomes of sepsis and whether there were differences in survival across treatment arms for patients with different baseline biomarker profiles. DESIGN: Secondary analysis of a large randomized clinical trial...
January 10, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28076818/one-way-allosteric-communication-between-the-two-disulfide-bonds-in-tissue-factor
#5
Beifei Zhou, Philip J Hogg, Frauke Gräter
Tissue factor (TF) is a transmembrane glycoprotein that plays distinct roles in the initiation of extrinsic coagulation cascade and thrombosis. TF contains two disulfide bonds, one each in the N-terminal and C-terminal extracellular domains. The C-domain disulfide, Cys186-Cys209, has a -RHStaple configuration in crystal structures, suggesting that this disulfide carries high pre-stress. The redox state of this disulfide has been proposed to regulate TF encryption/decryption. Ablating the N-domain Cys49-Cys57 disulfide bond was found to increase the redox potential of the Cys186-Cys209 bond, implying an allosteric communication between the domains...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28074087/the-genetic-variation-rs6903956-in-the-novel-androgen-dependent-tissue-factor-pathway-inhibitor-regulating-protein-adtrp-gene-is-not-associated-with-levels-of-plasma-coagulation-factors-in-the-singaporean-chinese
#6
Xuling Chang, Hui-Lin Chin, Swee-Chye Quek, Daniel Y T Goh, Rajkumar Dorajoo, Yechiel Friedlander, Chew-Kiat Heng
BACKGROUND: Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population. Although ADTRP is believed to be involved in the upregulation of TFPI, the underlying mechanism involved is largely unknown. This study investigated the association of rs6903956 with plasma Factor VII coagulant activity (FVIIc) and fibrinogen levels, which are regulated by TFPI and are independent risk predictors for CAD...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28069642/alpha-1-antitrypsin-enhances-islet-engraftment-by-suppression-of-instant-blood-mediated-inflammatory-reaction
#7
Jingjing Wang, Zhen Sun, Wenyu Gou, David B Adams, Wanxing Cui, Katherine A Morgan, Charlie Strange, Hongjun Wang
Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that alpha-1 antitrypsin (AAT, Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared to mice treated with saline...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28065270/functional-study-of-the-vitamin-k-cycle-enzymes-in-live-cells
#8
J-K Tie, D W Stafford
Vitamin K-dependent carboxylation, an essential posttranslational modification catalyzed by gamma-glutamyl carboxylase, is required for the biological functions of proteins that control blood coagulation, vascular calcification, bone metabolism, and other important physiological processes. Concomitant with carboxylation, reduced vitamin K (KH2) is oxidized to vitamin K epoxide (KO). KO must be recycled back to KH2 by the enzymes vitamin K epoxide reductase and vitamin K reductase in a pathway known as the vitamin K cycle...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28065164/plasma-proteome-and-metabolome-characterization-of-an-experimental-human-thyrotoxicosis-model
#9
Maik Pietzner, Beatrice Engelmann, Tim Kacprowski, Janine Golchert, Anna-Luise Dirk, Elke Hammer, K Alexander Iwen, Matthias Nauck, Henri Wallaschofski, Dagmar Führer, Thomas F Münte, Nele Friedrich, Uwe Völker, Georg Homuth, Georg Brabant
BACKGROUND: Determinations of thyrotropin (TSH) and free thyroxine (FT4) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT4-associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model. METHODS: A sample of 16 healthy young men were treated with levothyroxine for 8 weeks and plasma was sampled before the intake was started as well as at two points during treatment and after its completion, respectively...
January 9, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28059082/nmr-reveals-a-dynamic-allosteric-pathway-in-thrombin
#10
Lindsey D Handley, Brian Fuglestad, Kyle Stearns, Marco Tonelli, R Bryn Fenwick, Phineus R L Markwick, Elizabeth A Komives
Although serine proteases are found ubiquitously in both eukaryotes and prokaryotes, and they comprise the largest of all of the peptidase families, their dynamic motions remain obscure. The backbone dynamics of the coagulation serine protease, apo-thrombin (S195M-thrombin), were compared to the substrate-bound form (PPACK-thrombin). R1, R2, (15)N-{(1)H}NOEs, and relaxation dispersion NMR experiments were measured to capture motions across the ps to ms timescale. The ps-ns motions were not significantly altered upon substrate binding...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28058802/increased-thrombin-generation-in-a-mouse-model-of-cancer-cachexia-is-partially-interleukin-6-dependent
#11
Caroline J Reddel, John D Allen, Anahid Ehteda, Ryland Taylor, Vivien M Y Chen, Jennifer L Curnow, Leonard Kritharides, Graham Robertson
BACKGROUND: Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. OBJECTIVES: To assess if cancer cachexia altered coagulation state and if this was attributable to tumor IL-6 production...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28053193/promyelocytic-extracellular-chromatin-exacerbates-coagulation-and-fibrinolysis-in-acute-promyelocytic-leukemia
#12
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death due to hemorrhage remains unacceptably common and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28052038/competing-endogenous-rna-network-analysis-identifies-critical-genes-among-the-different-breast-cancer-subtypes
#13
Juan Chen, Juan Xu, Yongsheng Li, Jinwen Zhang, Hong Chen, Jianping Lu, Zishan Wang, Xueying Zhao, Kang Xu, Yixue Li, Xia Li, Yan Zhang
Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28045547/peptide-macrocycle-inhibitor-of-coagulation-factor-xii-with-subnanomolar-affinity-and-high-target-selectivity
#14
Simon Jan Middendorp, Jonas Wilbs, Claudia Quarroz, Sara Calzavarini, Anne Angelillo-Scherrer, Christian Heinis
Factor XII (FXII) is a plasma protease that has emerged in recent years as a potential target to treat or prevent pathological thrombosis, to inhibit contact activation in extracorporeal circulation, and to treat the swelling disorder hereditary angioedema. While several protein based inhibitors with high affinity for activated FXII (FXIIa) were developed, the generation of small molecule inhibitors has been challenging. In this work, we have generated a potent and selective FXIIa inhibitor by optimizing a peptide macrocycle that was recently evolved by phage display (Ki = 0...
January 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28043040/rho-kinase-inhibitor-treatment-prevents-pulmonary-inflammation-and-coagulation-in-lipopolysaccharide-induced-lung-injury
#15
Renyu Ding, Dongmei Zhao, Xiaoxia Li, Baoyan Liu, Xiaochun Ma
INTRODUCTION: In the pathogenesis of sepsis-induced acute lung injury (ALI), the crosstalk between inflammation and coagulation plays a pivotal role. The aim of this study was to investigate the role of Rho kinase (ROCK) inhibitor in alleviating pulmonary inflammation and coagulation in lipopolysaccharide (LPS)-induced acute lung injury (ALI) models. METHODS: In the in vivo study, mice were randomized to four different groups: Control, Y-27632 (Y), LPS, and LPS+Y-27632 (LPS+Y)...
December 24, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/28035007/inhibition-of-factor-xia-reduces-the-frequency-of-cerebral-microembolic-signals-derived-from-carotid-arterial-thrombosis-in-rabbits
#16
Xinkang Wang, Stan Kurowsk, Weizhen Wu, Gino A Castriota, Xueping Zhou, Lin Chu, Kenneth P Ellsworth, Scott Edmondson, Donald Chu, Amjad Ali, Patrick Andre, Dietmar Seiffert, Mark Erion, David E Gutstein, Zhu Chen
Factor XI (FXI) is an integral component of the intrinsic pathway of the coagulation cascade and plays a critical role in thrombus formation. Since its role in the pathogenesis of cerebral microembolic signals (MES) is unclear, this study utilized a potent and selective small molecule inhibitor of FXIa, Compound 1, to assess the effect of FXI blockade in our recently established preclinical model of cerebral MES induced by FeCl3 injury of the carotid artery in male New Zealand White rabbits. Ascending doses of Compound 1 were evaluated simultaneously for both carotid arterial thrombosis by a Doppler flowmeter and MES in the middle cerebral artery by a transcranial Doppler...
December 29, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28032527/bioreactivity-of-stent-material-activation-of-platelets-coagulation-leukocytes-and-endothelial-cell-dysfunction-in-vitro
#17
Veronique Ollivier, Caroline Roques, Nicolas Receveur, Matthias Gratz, Laurent Feldman, Didier Letourneur, Christian Gachet, Pierre H Mangin, Martine Jandrot-Perrus
Outcome of patients with coronary artery disease has been significantly improved by percutaneous coronary interventions with stent implantation. However, despite progress made on devices and antithrombotic treatments, stent thrombosis remains an important issue because of serious adverse consequences. Several mechanisms are assumed to favor stent thrombosis as platelet aggregation, fibrin formation, defective healing and local inflammation. The objective of this study was to evaluate in vitro the thrombogenicity, proinflammatory properties and healing capacities of cobalt-chromium (CoCr), an alloy commonly used for cardiovascular implants...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28018685/coexistence-of-factor-vii-deficiency-and-hereditary-spastic-paraplegia-in-two-siblings
#18
Hortensia De la Corte-Rodriguez, E Carlos Rodriguez-Merchan, M Teresa Alvarez-Roman, Ana L Hernandez-Moreno
We present the case of two patients aged 12 years and 7 years who were referred to our hospital for factor VII deficiency inherited in an autosomal recessive pattern, who had suffered from previous multiple joint haemarthroses. They presented with fine motor symptoms and difficulty in walking. During physical examination we observed neurological symptoms (general hypotonia, muscular hypotrophy, exaggerated tendon reflexes, pes cavus, and spastic gait). Given that the symptoms were not justified by the deficiency of coagulation factor VII and on suspicion of hereditary spastic paraplegia (HSP), tests were carried out...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/28017776/nobiletin-inhibits-oxidized-ldl-mediated-expression-of-tissue-factor-in-human-endothelial-cells-through-inhibition-of-nf-kb
#19
Plinio Cirillo, Stefano Conte, Giovanni Cimmino, Grazia Pellegrino, Francesca Ziviello, Giusi Barra, Ferdinando Carlo Sasso, Francesco Borgia, Raffaele De Palma, Bruno Trimarco
INTRODUCTION: Flavonoids are nutrients usually included in human diet with several significant biological activities. Nobiletin is a flavonoid that, besides having anti-inflammatory and anti-tumoral activity, seems to exert protective effects on cardiovascular system. Several studies investigated nobiletin as a natural drug to antagonize the atherosclerotic disease. On the contrary, literature about its potential role in modulating the main acute complication of atherosclerosis, thrombosis, is still scanty...
December 22, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28007958/polyphosphate-and-rna-differentially-modulate-the-contact-pathway-of-blood-clotting
#20
Joshua M Gajsiewicz, Stephanie A Smith, James H Morrissey
The contact pathway of the plasma clotting cascade is dispensable for normal hemostasis, but contributes to thrombosis and serves as a bridge between inflammation and coagulation. This pathway is triggered upon exposure of plasma to certain anionic polymers and artificial surfaces. Recently, extracellular nucleic acids and inorganic polyphosphate (polyP) have been implicated as being important (patho)physiologically relevant activators of this pathway. However, mechanistic details regarding how nucleic acids or polyP modulate the individual reactions of the contact pathway have been lacking...
December 22, 2016: Journal of Biological Chemistry
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