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Von Willebrand Factor

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https://www.readbyqxmd.com/read/28109051/shear-induced-platelet-aggregation-and-distribution-of-thrombogenesis-at-stenotic-vessels
#1
Hiroki Kamada, Yohsuke Imai, Masanori Nakamura, Takuji Ishikawa, Takami Yamaguchi
OBJECTIVE: Shear-induced platelet aggregation (SIPA), which is mediated by von Willebrand factor (vWF), is a key mechanism in arterial thrombosis under an abnormally high shear rate of blood flow. We investigated the influence of SIPA on thrombogenesis, focusing on alterations in blood flow at stenotic vessels. METHODS: We carried out a computer simulation of thrombogenesis in stenotic vessels at three different injury positions (i.e., upstream, apex, and downstream of the stenosis) to evaluate the effect of SIPA...
January 21, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28109042/expression-and-characterization-of-a-codon-optimized-blood-coagulation-factor-viii
#2
S A Shestopal, J-J Hao, E Karnaukhova, Y Liang, M V Ovanesov, M Lin, J H Kurasawa, T K Lee, J H McVey, A G Sarafanov
BACKGROUND: Production of recombinant factor VIII (FVIII) is challenging due to its low expression. It was previously shown that codon-optimization of a B domain-deleted FVIII (BDD-FVIII) cDNA resulted in increased protein expression. However, it is well-recognized that synonymous mutations may affect the protein structure and function. OBJECTIVES: To compare biochemical properties of a BDD-FVIII expressed from codon-optimized (CO) and the wild-type (WT) cDNAs. METHODS: Each variant of the BDD-FVIII was expressed in several independent CHO cell lines, generated using a lentiviral platform...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28104746/origin-and-evolution-of-the-sponge-aggregation-factor-gene-family
#3
Laura F Grice, Marie E A Gauthier, Kathrein E Roper, Xavier Fernàndez-Busquets, Sandie M Degnan, Bernard M Degnan
Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here we characterise the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic...
January 19, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28102428/plasma-adamts13-activity-and-von-willebrand-factor-antigen-and-activity-in-patients-with-subarachnoid-haemorrhage
#4
Monisha Kumar, Wenjing Cao, Jenny K McDaniel, Huy P Pham, Dheeraj Raju, Kelsey Nawalinski, Suzanne Frangos, David Kung, Eric Zager, Scott E Kasner, Joshua M Levine, X Long Zheng
Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). It was our objective to determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Forty consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls...
January 19, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28099190/coagulation-imbalance-and-neurocognitive-functioning-in-older-hiv-adults-on-suppressive-antiretroviral-therapy
#5
Jessica L Montoya, Jennifer Iudicello, Hannah A Oppenheim, Pariya L Fazeli, Michael Potter, Qing Ma, Paul J Mills, Ronald J Ellis, Igor Grant, Scott L Letendre, David J Moore
OBJECTIVES: To compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. DESIGN: Cross-sectional study of 66 antiretroviral therapy-treated virally suppressed HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. METHODS: Participants completed standardized neurobehavioral and neuromedical assessments...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28098417/delivery-of-anesthesia-for-children-with-mucopolysaccharidosis-type-iii-sanfilippo-syndrome-a-review-of-86-anesthetics
#6
Marc A Cohen, Grant M Stuart
BACKGROUND: Sanfilippo syndrome (MPS III) is rare, with 97 cases in the United Kingdom between 1988 and 1998. Mucopolysaccharide infiltration of tissues in mucopolysaccharidosis (MPS) causes multi-systemic pathology including difficult airways and cardiac disease. Published anesthesia case reviews of Sanfilippo syndrome have included limited numbers of patients to date. AIM: To identify the perioperative management and complications of anesthesia in children with mucopolysaccharidosis Type III at Great Ormond Street Hospital...
January 18, 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28091443/molecular-characterization-of-exon-28-of-von-willebrand-s-factor-gene-in-nigerian-population
#7
E D Ezigbo, E O Ukaejiofo, T U Nwagha
BACKGROUND: Polymorphisms in von Willebrand factor (VWF) gene are an important contributor to the expression of VWF gene and differences in ethnic distribution of these single nucleotide polymorphisms (SNPs) exists. AIMS: Our objective was to molecularly characterize the exon 28 of the VWF gene in the three major ethnic groups of Nigeria. SUBJECTS AND METHODS: We recruited 90 subjects, 45 had a history of bleeding. Questions included those used in the Zimmerman Program for the Molecular and Clinical Biology of von Willebrand disease (VWD), and the bleeding scores were calculated using the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD scoring system...
February 2017: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/28090741/conformational-quiescence-of-adamts13-prevents-proteolytic-promiscuity-reply
#8
K South, M O Freitas, D A Lane
We thank Drs Cao and Long Zheng for their interest in our paper recently published in JTH [1] in which we reported our findings that C-terminally truncated variants of ADAMTS13 directly cleave the Aα chain of fibrinogen. We postulated that conformationally activated ADAMTS13 [2, 3]may be able to cleave substrate(s) in addition to its usual substrate, the A2 domain of von Willebrand factor (VWF). In their letter, Cao and Long Zheng report that rather than cleaving fibrinogen directly, ADAMTS13 variants act indirectly, activating plasminogen, a common contaminant in commercial fibrinogen preparations...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28090594/effects-of-tranexamic-acid-on-platelet-function-and-thrombin-generation-etaplat-woman-trial-sub-study
#9
Kastriot Dallaku, Haleema Shakur, Ian Roberts, Phil Edwards, Danielle Beaumont, Maria Delius, Braun Siegmund, Orion Gliozheni, Ilir Tasha, Saimir Cenameri, Ulrich Mansmann
Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets.  Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH.  Methods. We will conduct a sub-study within the WOMAN trial...
December 15, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/28088607/transcatheter-aortic-valve-implantation-leads-to-a-restoration-of-von-willebrand-factor-vwf-abnormalities-in-patients-with-severe-aortic-stenosis-incidence-and-relevance-of-clinical-and-subclinical-vwf-dysfunction-in-patients-undergoing-transfemoral-tavi
#10
Alexander Sedaghat, Hannah Kulka, Jan-Malte Sinning, Nora Falkenberg, Julia Driesen, Barbara Preisler, Christoph Hammerstingl, Georg Nickenig, Bernd Pötzsch, Johannes Oldenburg, Hans-Jörg Hertfelder, Nikos Werner
BACKGROUND: In this study, we sought to analyze the incidence and relevance of von Willebrand factor (VWF) abnormalities in patients undergoing transcatheter aortic valve implantation (TAVI), especially on perioperative bleeding. Furthermore, we hypothesized that, similar to aortic valve surgery, TAVI results in a restoration of VWF abnormalities. METHODS AND RESULTS: We performed a prospective analysis of periinterventional VWF parameters in 74 patients (80±7years, female in 37...
January 7, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28087247/activity-of-von-willebrand-factor-and-levels-of-vwf-cleaving-protease-adamts13-in-preterm-and-full-term-neonates
#11
T Strauss, N Elisha, B Ravid, N Rosenberg, A Lubetsky, S Levy-Mendelovich, I Morag, U Nowak Göttl, G Kenet
Von Willebrand Factor (VWF) has a central role in primary hemostasis. Its biological activity is related to the size of VWF multimers, spontaneously binding to platelets and inducing circulating microthrombi formation. This process is down-regulated by the VWF cleaving protease ADAMTS13 (A Disintegrin and Metalloprotease with ThromboSpondin motif). To date, information regarding the levels of ADAMTS13 in neonates and preterm infants is scarce. Our aim was to study ADAMTS13, VWF antigen (Ag) and Ristocetin cofactor (RiCof) activity in neonates and evaluate potential correlations with perinatal complications...
December 29, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28076816/mutation-g1629e-increases-von-willebrand-factor-cleavage-via-a-cooperative-destabilization-mechanism
#12
Camilo Aponte-Santamaría, Svenja Lippok, Judith J Mittag, Tobias Obser, Reinhard Schneppenheim, Carsten Baldauf, Frauke Gräter, Ulrich Budde, Joachim O Rädler
The large multimeric glycoprotein von Willebrand Factor (VWF) plays a pivotal adhesive role during primary hemostasis. VWF is cleaved by the protease ADAMTS13 as a down-regulatory mechanism to prevent excessive VWF-mediated platelet aggregation. For each VWF monomer, the ADAMTS13 cleavage site is located deeply buried inside the VWF A2 domain. External forces in vivo or denaturants in vitro trigger the unfolding of this domain, thereby leaving the cleavage site solvent-exposed and ready for cleavage. Mutations in the VWF A2 domain, facilitating the cleavage process, cause a distinct form of von Willebrand disease (VWD), VWD type 2A...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28071872/mutant-botrocetin-2-inhibits-von-willebrand-factor-induced-platelet-agglutination
#13
T Matsui, A Hori, J Hamako, F Matsushita, Y Ozeki, Y Sakurai, M Hayakawa, M Matsumoto, Y Fujimura
BACKGROUND: Botrocetin-2 (Bot2) is a botrocetin-like protein composed of α and β subunits that have been cloned from the snake Bothrops jararaca. Bot2 binds specifically to von Willebrand factor (VWF), and the complex induces glycoprotein (GP) Ib-dependent platelet agglutination. OBJECTIVES: We exploited Bot2's VWF-binding capacity to try and create a mutant Bot2 that binds to VWF but inhibits platelet agglutination. METHODS AND RESULTS: Several point mutations were introduced into Bot2 cDNA, and the recombinant protein (rBot2) was purified on an anti-botrocetin column...
January 10, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28067100/effects-of-a-single-bout-of-strenuous-exercise-on-platelet-activation-in-female-apoe-ldlr-mice
#14
K Przyborowski, H Kassassir, M Wojewoda, K Kmiecik, B Sitek, K Siewiera, A Zakrzewska, A M Rudolf, R Kostogrys, C Watala, J A Zoladz, S Chlopicki
Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI2) and nitric oxide (NO). However, in the case of endothelial dysfunction, e.g. in atherosclerosis, there exists an increased risk for intravascular thrombosis during exercise that might be due to an impairment in endothelial anti-platelet mechanisms. In the present work, we evaluated platelet activation at rest and following a single bout of strenuous treadmill exercise in female ApoE/LDLR(-)(/-) mice with early (3-month-old) and advanced (7-month-old) atherosclerosis compared to female age-matched WT mice...
January 9, 2017: Platelets
https://www.readbyqxmd.com/read/28065360/intracavernous-injection-of-human-umbilical-cord-blood-mononuclear-cells-improves-erectile-dysfunction-in-streptozotocin-induced-diabetic-rats
#15
Tugba Cengiz, Ecem Kaya, Didem Yilmaz Oral, Isil Ozakca, Nur Bayatli, Arzu Zeynep Karabay, Tugba Altun Ensari, Tuna Karahan, Enis Yilmaz, Serap Gur
INTRODUCTION: Erectile dysfunction (ED) worsens in men with diabetes. Human umbilical cord blood (HUCB), because of its widespread availability and low immunogenicity, is a valuable source for stem cell-based therapies. AIM: To determine the effect of intracavernous injection of HUCB mononuclear cells (MNCs) on ED in rats with diabetes induced by streptozotocin. METHODS: Thirty adult male Sprague-Dawley rats were equally divided into three groups: (i) control, (ii) diabetes induced by streptozotocin (35 mg/kg intravenously for 8 weeks), and (iii) diabetic rats treated with MNCs (1 × 10(6) cells by intracavernosal injection)...
January 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28062498/novel-thrombotic-function-of-a-human-snp-in-stxbp5-revealed-by-crispr-cas9-gene-editing-in-mice
#16
Qiuyu Martin Zhu, Kyung Ae Ko, Sara Ture, Michael A Mastrangelo, Ming-Huei Chen, Andrew D Johnson, Christopher J O'Donnell, Craig N Morrell, Joseph M Miano, Charles J Lowenstein
OBJECTIVE: To identify and characterize the effect of a SNP (single-nucleotide polymorphism) in the STXBP5 locus that is associated with altered thrombosis in humans. GWASs (genome-wide association studies) have identified numerous SNPs associated with human thrombotic phenotypes, but determining the functional significance of an individual candidate SNP can be challenging, particularly when in vivo modeling is required. Recent GWAS led to the discovery of STXBP5 as a regulator of platelet secretion in humans...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28059438/optimized-method-for-isolating-highly-purified-and-functional-porcine-aortic-endothelial-and-smooth-muscle-cells
#17
Farideh Beigi, Mitalben Patel, Marco A Morales-Garza, Caitlin Winebrenner, Andrea S Gobin, Eric Chau, Luiz C Sampaio, Doris A Taylor
BACKGROUND: Numerous protocols exist for isolating aortic endothelial and smooth muscle cells from small animals. However, establishing a protocol for isolating pure cell populations from large animal vessels that are more elastic has been challenging. We developed a simple sequential enzymatic approach to isolate highly purified populations of porcine aortic endothelial and smooth muscle cells. METHODS: The lumen of a porcine aorta was filled with 25 U/mL dispase solution and incubated at 37°C to dissociate the endothelial cells...
January 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28057741/factor-viii-v-c-domain-swaps-reveal-discrete-c-domain-roles-in-factor-viii-function-and-intracellular-trafficking
#18
Eduard H T M Ebberink, Eveline A M Bouwens, Esther Bloem, Mariëtte Boon-Spijker, Maartje Van den Biggelaar, Jan Voorberg, Alexander B Meijer, Koen Mertens
Factor VIII C-domains are believed to contain specific function in co-factor activity and in interaction with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study we furthermore addressed the contribution of individual factor VIII C-domains in intracellular targeting, von Willebrand factor binding and co-factor activity by factor VIII/V C-domain swapping...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28055145/conformational-quiescence-of-adamts13-prevents-proteolytic-promiscuity-comment
#19
W J Cao, X L Zheng
Von Willebrand factor (VWF) is the only substrate identified for ADAMTS13 to date [1]. How ADAMTS13 achieves such remarkable substrate specificity remains a mystery. Previous studies demonstrated that carboxyl-terminal domains including 2-8(th) thrombospondin type 1 repeat (TSP1) and CUB domains are dispensable for cleavage of VWF substrate under various conditions [2, 3]. However, these carboxyl-terminal domains were later found to exhibit a disulfide bond reducing activity [4] and to interact with globular VWF via its D4 domain [5]...
January 5, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28043678/associations-between-blood-coagulation-markers-nt-probnp-and-risk-of-incident-heart-failure-in-older-men-the-british-regional-heart-study
#20
S Goya Wannamethee, Peter H Whincup, Olia Papacosta, Lucy Lennon, Gordon D Lowe
AIMS: Chronic heart failure (HF) is associated with activation of blood coagulation but there is a lack of prospective studies on the association between coagulation markers and incident HF in general populations. We have examined the association between the coagulation markers fibrinogen, von Willebrand Factor (VWF), Factors VII, VIII and IX, D-dimer, activated protein C (APC) and activated partial thromboplastin time (aPPT) with NT-proBNP and incident HF. METHODS AND RESULTS: Prospective study of 3366 men aged 60-79years with no prevalent HF, myocardial infarction or venous thrombosis and who were not on warfarin, followed up for a mean period of 13years, in whom there were 203 incident HF cases...
December 20, 2016: International Journal of Cardiology
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