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Coagulation cascade

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https://www.readbyqxmd.com/read/28104608/prothrombin-loading-of-vascular-smooth-muscle-cell-derived-exosomes-regulates-coagulation-and-calcification
#1
Alexander N Kapustin, Michael Schoppet, Leon J Schurgers, Joanne L Reynolds, Rosamund McNair, Alexander Heiss, Willi Jahnen-Dechent, Tilman M Hackeng, Georg Schlieper, Paul Harrison, Catherine M Shanahan
OBJECTIVE: The drug warfarin blocks carboxylation of vitamin K-dependent proteins and acts as an anticoagulant and an accelerant of vascular calcification. The calcification inhibitor MGP (matrix Gla [carboxyglutamic acid] protein), produced by vascular smooth muscle cells (VSMCs), is a key target of warfarin action in promoting calcification; however, it remains unclear whether proteins in the coagulation cascade also play a role in calcification. APPROACH AND RESULTS: Vascular calcification is initiated by exosomes, and proteomic analysis revealed that VSMC exosomes are loaded with Gla-containing coagulation factors: IX and X, PT (prothrombin), and proteins C and S...
January 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28102737/platelet-microvesicles-in-health-and-disease
#2
Imene Melki, Nicolas Tessandier, Anne Zufferey, Eric Boilard
Interest in cell-derived extracellular vesicles and their physiological and pathological implications is constantly growing. Microvesicles, also known as microparticles, are small extracellular vesicles released by cells in response to activation or apoptosis. Among the different microvesicles present in the blood of healthy individuals, platelet-derived microvesicles (PMVs) are the most abundant. Their characterization has revealed a heterogeneous cargo that includes a set of adhesion molecules. Similarly to platelets, PMVs are also involved in thrombosis through support of the coagulation cascade...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28095402/a-general-shear-dependent-model-for-thrombus-formation
#3
Alireza Yazdani, He Li, Jay D Humphrey, George Em Karniadakis
Modeling the transport, activation, and adhesion of platelets is crucial in predicting thrombus formation and growth following a thrombotic event in normal or pathological conditions. We propose a shear-dependent platelet adhesive model based on the Morse potential that is calibrated by existing in vivo and in vitro experimental data and can be used over a wide range of flow shear rates ([Formula: see text]). We introduce an Eulerian-Lagrangian model where hemodynamics is solved on a fixed Eulerian grid, while platelets are tracked using a Lagrangian framework...
January 2017: PLoS Computational Biology
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
#4
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/28079978/targeting-coagulation-factor-receptors-protease-activated-receptors-in-idiopathic-pulmonary-fibrosis
#5
REVIEW
Cong Lin, Keren Borensztajn, C Arnold Spek
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a 5-year mortality rate above 50% and unknown etiology. Treatment options remain limited and, currently, only two drugs are available, nintedanib and pirfenidone. However, both of these antifibrotic agents only slow down the progression of the disease but do not remarkably prolong the survival of IPF patients. Hence, the discovery of new therapeutic targets for IPF is crucial. Studies exploring the mechanisms that are involved in IPF identified several possible targets for therapeutic interventions...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079789/the-impact-of-irrigating-fluid-absorption-on-blood-coagulation-in-patients-undergoing-transurethral-resection-of-the-prostate-a-prospective-observational-study-using-rotational-thromboelastometry
#6
Hyun-Jung Shin, Hyo-Seok Na, Young-Tae Jeon, Hee-Pyoung Park, Sun-Woo Nam, Jung-Won Hwang
Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM).A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol-0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28076818/one-way-allosteric-communication-between-the-two-disulfide-bonds-in-tissue-factor
#7
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/28042080/heparin-coatings-for-improving-blood-compatibility-of-medical-devices
#8
REVIEW
Roy Biran, Daniel Pond
Blood contact with biomaterials triggers activation of multiple reactive mechanisms that can impair the performance of implantable medical devices and potentially cause serious adverse clinical events. This includes thrombosis and thromboembolic complications due to activation of platelets and the coagulation cascade, activation of the complement system, and inflammation. Numerous surface coatings have been developed to improve blood compatibility of biomaterials. For more than thirty years, the anticoagulant drug heparin has been employed as a covalently immobilized surface coating on a variety of medical devices...
December 29, 2016: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28035007/inhibition-of-factor-xia-reduces-the-frequency-of-cerebral-microembolic-signals-derived-from-carotid-arterial-thrombosis-in-rabbits
#9
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/28025140/protease-activated-receptor-2-exacerbates-adenine-induced-renal-tubulointerstitial-injury-in-mice
#10
Sakiko Hayashi, Yuji Oe, Tomofumi Fushima, Emiko Sato, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi
Hypercoagulability is associated with chronic kidney disease (CKD). Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade are known to activate protease-activated receptor 2 (PAR2), and to cause inflammation and tissue injury. Although PAR2 is highly expressed in the kidney, it is unclear whether PAR2 plays a pathogenic role in CKD. To test this, we fed the mice lacking Par2 (F2rl1(-/-)) and wild type (F2rl1(+/+)) mice with adenine diet to induce tubulointerstitial injury, a hallmark of CKD...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28007958/polyphosphate-and-rna-differentially-modulate-the-contact-pathway-of-blood-clotting
#11
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
https://www.readbyqxmd.com/read/28005926/the-central-role-of-kng1-gene-as-a-genetic-determinant-of-coagulation-pathway-related-traits-exploring-metaphenotypes
#12
Helena Brunel, Raimon Massanet, Angel Martinez-Perez, Andrey Ziyatdinov, Laura Martin-Fernandez, Juan Carlos Souto, Alexandre Perera, José Manuel Soria
Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i...
2016: PloS One
https://www.readbyqxmd.com/read/27990282/the-complement-system-an-evolution-in-progress
#13
REVIEW
Berhane Ghebrehiwet
The complement system, which consists of three independent but interacting pathways, constitutes a powerful arm of innate immunity. Its major function is to recognize and destroy pathogenic microorganisms as well as eliminate modified self-antigens. Although it is a fine-tuned system with innate capacity to discriminate self from non-self as well as danger from non-danger signals, an unwarranted activation can nonetheless occur and cause tissue destruction. To prevent such activation, specific regulators present both in plasma and on the cell surface tightly control it...
2016: F1000Research
https://www.readbyqxmd.com/read/27980224/influence-of-aging-on-the-activity-of-mice-sca-1-cd31-cardiac-stem-cells
#14
Qiong Wu, Jinxi Zhan, Shiming Pu, Liu Qin, Yun Li, Zuping Zhou
Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31- subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done...
December 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27979702/quercetin-and-baicalein-suppress-monocrotaline-induced-hepatic-sinusoidal-obstruction-syndrome-in-rats
#15
Jiaqi Zhang, Yuchen Sheng, Liang Shi, Zhiyong Zheng, Minwei Chen, Bin Lu, Lili Ji
Hepatic sinusoidal obstruction syndrome (SOS) is a rare liver disease with considerable mortality. This study is designed to observe the protection of quercetin and baicalein against monocrotaline (MCT)-induced SOS in rats and its engaged mechanism. Rats were pre-administrated with MCT (90mg/kg) to induce SOS, and 6, 30h later were orally given with quercetin and baicalein (40mg/kg) twice. Results of detecting rats with liver ascites, measuring serum transaminases, total bilirubin (TBil) and bile acids (TBA), analyzing blood cells, liver histological evaluation and scanning electron microscope observation all demonstrated the detoxification of quercetin and baicalein against MCT-induced SOS in rats...
December 13, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27966324/the-effect-of-pneumoperitoneum-on-intravascular-fibrinolytic-activity-in-rats
#16
Kürşat Dikmen, Asiye Uğraş Dikmen, Hasan Bostancı, Ahmet Karamercan, Münci Yağcı, Murat Akın, Bülent Aytaç
BACKGROUND/AIM: Venous stasis during pneumoperitoneum in laparoscopic surgery is closely related to fibrin synthesis and deposition. The etiologic factors underlying fibrinolysis or hypercoagulability are not clearly defined. This study aimed to determine the effects of pneumoperitoneum time and pressure on coagulation cascade and the fibrinolytic pathway. MATERIALS AND METHODS: After the pneumoperitoneum model was established in rats, PAI-1, tPA, TAFI, D-dimer, and fibrinogen activities were evaluated in different time periods under different pressures in groups including 6 rats...
November 17, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/27965162/transcriptome-profiling-of-developing-spleen-tissue-and-discovery-of-immune-related-genes-in-grass-carp-ctenopharyngodon-idella
#17
Guoxi Li, Yinli Zhao, Jie Wang, Bianzhi Liu, Xiangli Sun, Shuang Guo, Jianxin Feng
Grass carp Ctenopharyngodon idella is an important freshwater aquaculture species. However, studies regarding transcriptomic profiling of developing spleen tissue in the grass carp are lacking. Here, the transcriptome sequencing from the spleen tissue of one-year-old (cis1) and three-year-old (cis3) grass carp was performed using Illumina paired-end sequencing technology. The de novo assemblies yielded 48,970 unigenes with average lengths of 1264.51 bp from the two libraries. The assembled unigenes were evaluated and functionally annotated by comparing with sequences in major public databases including Nr, COG, Swiss-Prot, KEGG, Pfam and GO...
December 11, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27965156/fibri-nogen-drives-repair-after-acetaminophen-induced-liver-injury-via-leukocyte-%C3%AE-m%C3%AE-2-integrin-dependent-upregulation-of-mmp12
#18
Anna K Kopec, Nikita Joshi, Holly Cline-Fedewa, Anna V Wojcicki, Jessica L Ray, Bradley P Sullivan, John E Froehlich, Brendan F Johnson, Matthew J Flick, James P Luyendyk
BACKGROUND & AIMS: Acetaminophen (APAP)-induced liver injury is coupled to activation of the blood coagulation cascade and fibrin(ogen) accumulation within APAP-injured livers of experimental mice. We sought to define the precise role of fibrin(ogen) deposition in APAP-induced liver injury and repair METHODS: Fasted mice were injected with 300 mg/kg APAP i.p. and evaluated various times later RESULTS: In wild-type mice APAP overdose increased intrahepatic levels of high molecular weight cross-linked fibrin(ogen)...
December 10, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27942785/-factor%C3%A2-xiii-pharmacodynamic-and-pharmacokinetic-characteristics
#19
E H Adam, S Kreuer, K Zacharowski, C F Weber, R Wildenauer
Factor XIII (FXIII) plays an important role in the field of blood coagulation. In the last decade, both congenital and acquired deficiencies have been investigated in clinical studies. FXIII is a versatile enzyme that leads to a covalent cross-linking of fibrin fibrils at the end of the clotting cascade and supports platelet adhesion to the damaged sub-endothelium with the result of a mechanically stable clot.Symptoms of FXIII deficiencies vary within a broad spectrum from superficial skin bleeding episodes to severe, sometimes life threatening hemorrhage, requiring prophylactic or therapeutic replacement therapy...
December 9, 2016: Der Anaesthesist
https://www.readbyqxmd.com/read/27941623/identification-of-potential-biomarkers-for-rhegmatogenous-retinal-detachment-associated-with-choroidal-detachment-by-vitreous-itraq-based-proteomic-profiling
#20
Zhifeng Wu, Nannan Ding, Mengxi Yu, Ke Wang, Shasha Luo, Wenjun Zou, Ying Zhou, Biao Yan, Qin Jiang
Rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) is a complicated and serious type of rhegmatogenous retinal detachment (RRD). In this study, we identified differentially expressed proteins in the vitreous humors of RRDCD and RRD using isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography-electrospray ion trap-mass spectrometry-mass spectrometry (nano-LC-ESI-MS/MS) and bioinformatic analysis. Our result shows that 103 differentially expressed proteins, including 54 up-regulated and 49 down-regulated proteins were identified in RRDCD...
December 7, 2016: International Journal of Molecular Sciences
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