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https://www.readbyqxmd.com/read/28546076/sirna-knockdown-of-adamts-13-modulates-endothelial-cell-angiogenesis
#1
Huiyuan Tang, Manfai Lee, Eun Ho Kim, Daniel Bishop, George M Rodgers
ADAMTS-13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a zinc-containing metalloprotease that cleaves von Willebrand factor (vWf). Previous publications by our laboratory have shown that ADAMTS-13 may also be involved in angiogenesis. For this study, we report the successful transient knockdown of endogenous ADAMTS-13 in human umbilical vein endothelial cells (HUVEC) via siRNA and the effects of reduced endogenous ADAMTS-13 on HUVEC angiogenesis functions. 15nM of ADAMTS-13 siRNA reduced HUVEC ADAMTS-13 protein levels by 90% after 24h incubation, whereas control siRNA did not affect endogenous ADAMTS-13 levels...
May 22, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28544236/clinical-and-laboratory-phenotype-variability-in-type-2m-von-willebrand-disease
#2
Ashley L Doruelo, Sandra L Haberichter, Pamela A Christopherson, Lisa N Boggio, Sweta Gupta, Steven R Lentz, Amy D Shapiro, Robert R Montgomery, Veronica H Flood
BACKGROUND: Von Willebrand factor (VWF) is a multimeric coagulation factor that tethers platelets to injured subendothelium. Type 2M von Willebrand Disease (VWD) is characterized by a qualitative defect in VWF with preserved multimer distribution. OBJECTIVES: Through the Zimmerman Program for the Molecular and Clinical Biology for VWD, five VWF sequence variations were studied in subjects diagnosed with type 2M VWD. METHODS: Bleeding phenotype was assessed using the ISTH bleeding assessment tool...
May 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28539283/-effect-of-globular-adiponectin-on-proliferation-migration-and-tube-formation-of-ovarian-microvascular-endothelial-cells
#3
Lei Chen, Xiao-Sheng Lu, Ya-Lan Li, Zhou-Fei Mao, Luan-Juan Xiao, Yan-Hong Yu
OBJECTIVE: To analyze the effect of globular adiponectin on angiogenesis of ovarian microvascular endothelial cells (OMECs). METHODS: Mouse OMECs were isolated and purified by density gradient centrifugation with Percoll and identified by immunofluorescence analysis of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), and endothelial cell marker von Willebrand factor (vWF). The capillary-like tube formation of OMECs was determined by vascular endothelial growth factor A (VEGFA) treatment in Matrigel matrix...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28536718/molecular-and-clinical-profile-of-vwd-in-a-large-cohort-of-chinese-population-application-of-next-generation-sequencing-and-cnvplex-%C3%A2-technique
#4
Qian Liang, Huanhuan Qin, Qiulan Ding, Xiaoling Xie, Runhui Wu, Hongli Wang, Yiqun Hu, Xuefeng Wang
Von Willebrand disease (VWD), the most common inherited bleeding disorder, is characterised by a variable bleeding tendency, heterogeneous laboratory phenotype and race specific distribution of mutations. The present study aimed to determine the correlation of genotype and phenotype in 200 Chinese individuals from 90 unrelated families with VWD. Next generation sequencing (NGS) of the whole coding VWF, copy number analysis of VWF by CNVplex® technique as well as a comprehensive phenotypic assessment were carried out in all index patients (IPs)...
May 24, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28533135/enhanced-local-disorder-in-a-clinically-elusive-von-willebrand-factor-provokes-high-affinity-platelet-clumping
#5
Alexander Tischer, Venkata R Machha, Juan P Frontroth, Maria A Brehm, Tobias Obser, Reinhard Schneppenheim, Leland Mayne, S Walter Englander, Matthew Auton
Mutation of the cysteines forming the disulfide loop of the platelet GPIbα adhesive A1 domain of von Willebrand factor causes quantitative VWF deficiencies in the blood and von Willebrand disease. We report two cases of transient severe thrombocytopenia induced by DDAVP-treatment. Cys1272Trp and Cys1458Tyr mutations identified by genetic sequencing implicate an abnormal gain-of-function phenotype, evidenced by thrombocytopenia, that quickly relapses back to normal platelet counts and deficient plasma VWF. Using surface plasmon resonance, analytical rheology, and hydrogen-deuterium exchange mass spectrometry (HXMS), we decipher mechanisms of A1-GPIbα mediated platelet adhesion and resolve dynamic secondary structure elements that regulate the binding pathway...
May 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28531772/diet-induced-weight-loss-and-markers-of-endothelial-dysfunction-and-inflammation-in-treated-patients-with-type-2-diabetes
#6
K A Berk, T P Oudshoorn, A J M Verhoeven, M T Mulder, A J M Roks, W A Dik, R Timman, E J G Sijbrands
BACKGROUND & AIMS: Overweight and obesity increase cardiovascular mortality in patients with type 2 diabetes (T2D). In a recent trial, however, diet-induced weight loss did not reduce the cardiovascular risk of patients with T2D, possibly due to the parallel intensive medical treatment. We investigated the effect of diet-induced weight loss on cardiovascular risk factors in overweight and obese patients with T2D, and whether this effect was influenced by the use of statins, ACE inhibitors, metformin and duration of T2D...
October 2016: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/28527913/von-willebrand-factor-deficiency-reduces-liver-fibrosis-in-mice
#7
Nikita Joshi, Anna K Kopec, Jessica L Ray, Holly Cline-Fedewa, Dafna J Groeneveld, Ton Lisman, James P Luyendyk
Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28526067/the-chimeric-monoclonal-antibody-mhcsz-123-against-human-von-willebrand-factor-a3-domain-inhibits-high-shear-arterial-thrombosis-in-a-rhesus-monkey-model
#8
Shundong Ji, Miao Jiang, Bin Yan, Fei Shen, Yang He, Aini Wan, Lijun Xia, Changgeng Ruan, Yiming Zhao
BACKGROUND: SZ-123, a murine monoclonal antibody that targets the human von Willebrand factor (VWF) A3 domain and blocks the binding of collagen, is a powerful antithrombotic. In a Rhesus monkey model of thrombosis, SZ-123 had no side effects, such as bleeding or thrombocytopenia. METHODS: The mouse/human chimeric version of SZ-123, MHCSZ-123, was developed and maintained inhibitory capacities in vitro and ex vivo after injection into monkeys. CHO-S cells were selected for stable expression of MHCSZ-123...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28523822/development-of-a-novel-flow-cytometric-immunobead-array-to-quantify-vwf-ag-and-vwf-gpibr-and-its-application-in-acute-myocardial-infarction
#9
Bin Yan, Mengqiao Xu, Yunxiao Zhao, Haijun Guo, Lijun Xia, Changgeng Ruan, Yiming Zhao
OBJECTIVES: Both von Willebrand disease (VWD) and acute myocardial infarction (AMI) involve quantitative and qualitative changes in von Willebrand factor (VWF). Our objective was to develop a rapid and precise flow cytometric immunobead array (FCIA) to quantify VWF antigen (VWF:Ag) and ristocetin-triggered platelet glycoprotein Ib binding (VWF:GPIbR), and apply it in a clinical setting. METHODS: Microbeads, coated with monoclonal antibodies for SZ29 or SZ151 IgG, were incubated with diluted plasma...
May 18, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28514969/endothelial-progenitor-cell-number-is-not-decreased-in-34-children-with-juvenile-dermatomyositis-a-pilot-study
#10
Dong Xu, Akadia Kacha-Ochana, Gabrielle A Morgan, Chiang-Ching Huang, Lauren M Pachman
OBJECTIVE: A pilot study to determine endothelial progenitor cells (EPC) number in children with Juvenile Dermatomyositis (JDM). METHODS: After obtaining informed consent, the EPC number from 34 fasting children with definite/probable JDM at various stages of therapy-initially untreated, active disease on medication and clinically inactive, off medication-was compared with 13 healthy fasting pediatric controls. The EPC number was determined by fluorescence activated cell sorting (FACS), CD34(+)/VEGFR2(+)/CD45dim(-), and assessed in conjunction with clinical variables: disease activity scores (DAS), duration of untreated disease (DUD), TNF-α allelic polymorphism (A/G) at the promoter region of -308, number of nailfold capillary end row loop (ERL) and von Willebrand factor antigen (vWF:Ag)...
May 17, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28513999/microparticles-of-healthy-origins-improve-endothelial-progenitor-cell-dysfunction-via-microrna-transfer-in-an-atherosclerotic-hamster-model
#11
Nicoleta Alexandru, Eugen Andrei, Loredan Niculescu, Emanuel Dragan, Violeta Ristoiu, Adriana Georgescu
AIM: In this study we aimed: (1) to obtain and functionally characterize the cultures of late endothelial progenitor cells (EPCs) from the animal blood; (2) to investigate the potential beneficial effects of circulating microparticles (MPs) of healthy origins on EPC dysfunctionality in atherosclerosis as well as involved mechanisms. METHODS: Late EPCs were obtained and expanded in culture from peripheral blood isolated from two animal groups: hypertensive-hyperlipidemic (HH) and control (C) hamsters...
May 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28512557/increased-vasoocclusive-crises-in-o-blood-group-sickle-cell-disease-patients-association-with-underlying-thrombospondin-levels
#12
M Al Huneini, S Alkindi, V Panjwani, K Al Falahi, B Al Balushi, D Gravell, C H Ho, R Krishnamoorthy, A V Pathare
OBJECTIVES: To explore the incidence of vaso-occlusive crisis (VOC) in Blood Group "O" sickle cell disease (SCD) patients, and correlate it with the blood group and thrombospondin (TSP) levels. METHODS: In 89 consecutive SCD patients, blood samples were obtained for von Williebrand factor (vWF:Ag) antigen, collagen binding activity (CBA), ristocetin binding activity (RCo), blood group typing, C-reactive protein (CRP), high performance liquid chromatography (HPLC), Serum TSP 1 and TSP 2 levels, complete blood counts (CBC), lactic dehydrogenase (LDH) levels, liver function (LFT) and renal function tests (RFT) during VOC episodes and in steady state conditions...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28512017/a-case-of-autoimmune-severe-acquired-von-willebrand-syndrome-type-3-like
#13
Chakri Gavva, Prapti Patel, Yu-Min Shen, Eugene Frenkel, Ravi Sarode
Von Willebrand disease (VWD) is the most common congenital bleeding disorder and is due to quantitative or qualitative defects of von Willebrand factor (VWF). Acquired defects of VWF, termed acquired von Willebrand syndrome (AVWS), are due to a host of different mechanisms. Autoantibody-mediated AVWS may be associated with lymphoproliferative or immunological disorders, such as systemic lupus erythematosus (SLE). A large majority of AVWS cases are type 1 or type 2A-like and patients tend to have a mild to moderate bleeding tendency...
April 27, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28511390/expression-of-angiogenic-factors-in-psoriasis-vulgaris
#14
Lakshna Sankar, Dhanalakshmi Arumugam, Sudha Boj, Priyanka Pradeep
INTRODUCTION: Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, abnormal differentiation and inflammatory infiltration in the dermis. The dermal microvascular expansion associated with abnormal orientation and dilatation of capillaries in the biopsies of the psoriatic skin suggest that the disease is dependent on angiogenesis. AIM: To analyze and compare the immunohistochemical expression of angiogenic factors - Vascular Endothelial Growth Factor (VEGF), von Willebrand Factor (vWF) and CD 34 in skin biopsies of psoriasis cases with control skin samples; and to correlate the expression of angiogenic factors with Psoriasis Area and Severity Clinical Index (PASI SCORE)...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28503993/dual-inhibition-of-pi3k-and-mtor-by-vs-5584-suppresses-thrombus-formation
#15
Thomas Später, Isabelle Müller, Hermann Eichler, Michael D Menger, Matthias W Laschke, Emmanuel Ampofo
VS-5584 is a highly selective dual kinase inhibitor which suppresses phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) activity. Because these kinases are crucially involved in primary hemostasis, we herein investigated the effect of this compound on thrombus formation in vitro and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP) with VS-5584 inhibited the agonist-induced activation of surface glycoprotein complex (GP)IIb/IIIa and the upregulation of P-selectin...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28503498/evaluation-of-energy-balance-on-human-telomerase-reverse-transcriptase-htert-alternative-splicing-by-semi-quantitative-rt-pcr-in-human-umbilical-vein-endothelial-cells
#16
Mohaddeseh Behjati, Mohammad Hashemi, Mohammad Kazemi, Mansoor Salehi, Shaghayegh Haghjooy Javanmard
BACKGROUND: Decreased high-energy phosphate level is involved in endothelial cell injury and dysfunction. Reduced telomerase activity in endothelial cells in parallel with reduced energy levels might be due to altered direction of alternative splicing machine as a complication of depleted energy during the process of atherosclerosis. MATERIALS AND METHODS: Isolated human umbilical vein endothelial cells (HUVECs) were treated for 24 hours by oligomycine (OM) and 2-deoxy glucose (2-DG)...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28502501/apolipoprotein-b-vs-non-high-density-lipoprotein-cholesterol-association-with-endothelial-hemostatic-markers-and-carotid-intima-media-thickness
#17
David Karasek, Helena Vaverkova, Lubica Cibickova, Jaromira Gajdova, Veronika Kubickova
BACKGROUND: Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for lipid-lowering therapy, which correlate more strongly with cardiovascular events than low-density lipoprotein cholesterol. OBJECTIVE: The aim of this cross-sectional study was to evaluate the differences in plasma levels of plasminogen activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic marker for atherosclerotic vascular disease among dyslipidemic individuals with apoB levels higher, estimated or lower based on regression equation of apoB vs non-HDL-C...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28495930/adamts13-retards-progression-of-diabetic-nephropathy-by-inhibiting-intrarenal-thrombosis-in-mice
#18
Nirav Dhanesha, Prakash Doddapattar, Mehul R Chorawala, Manasa K Nayak, Koichi Kokame, Janice M Staber, Steven R Lentz, Anil K Chauhan
OBJECTIVE: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found association between reduced ADAMTS13-specific activity, ultralarge VWF multimers, and thrombotic angiopathy in patients with diabetic nephropathy. It remains unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a causative effect in diabetic nephropathy...
May 11, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28495826/genetic-drivers-of-von-willebrand-factor-levels-in-an-ischemic-stroke-population-and-association-with-risk-for-recurrent-stroke
#19
Stephen R Williams, Fang-Chi Hsu, Keith L Keene, Wei-Min Chen, Godfrey Dzhivhuho, Joe L Rowles, Andrew M Southerland, Karen L Furie, Stephen S Rich, Bradford B Worrall, Michèle M Sale
BACKGROUND AND PURPOSE: von Willebrand factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. METHODS: We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the VISP trial (Vitamin Intervention for Stroke Prevention) and the use of vWF in reclassification over traditional factors...
May 11, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28487393/potent-thrombolytic-effect-of-n-acetylcysteine-on-arterial-thrombi
#20
Sara Martinez de Lizarrondo, Clément Gakuba, Bradley A Herbig, Yohann Repessé, Carine Ali, Cécile V Denis, Peter Lenting, Emmanuel Touzé, Scott L Diamond, Denis Vivien, Maxime Gauberti
Background -Platelet crosslinking during arterial thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet-rich thrombi and restore vessel patency in acute thrombotic disorders such as ischemic stroke, acute coronary syndrome or acute limb ischemia. N-Acetylcysteine (NAC, a clinically approved mucolytic drug) can reduce intrachain disulfide bonds in large polymeric proteins. In the present study, we postulated that NAC might cleave the VWF multimers inside occlusive thrombi, thereby leading to their dissolution and arterial recanalization...
May 9, 2017: Circulation
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