Article
Biochemistry & Molecular Biology
Marcela Montilla, Isabel Atienza-Navarro, Francisco Jose Garcia-Cozar, Carmen Castro, Francisco Javier Rodriguez-Martorell, Felix A. Ruiz
Summary: Polyphosphate (polyP) plays an important modulatory role in the binding of von Willebrand factor (VWF) and Factor VIII (FVIII) in blood coagulation, and may be used in developing new therapies to activate VWF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Soracha Ward, Jamie M. O'Sullivan, James S. O'Donnell
Summary: Glycosylation is a crucial posttranslational modification that plays a key role in regulating protein biology with variations in glycan structures implicated in human diseases. The heavily glycosylated von Willebrand factor (VWF) with N- and O-linked glycans affecting its structure, function, and half-life, particularly highlighting the significant role of O-linked glycans in modulating VWF biology.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Article
Genetics & Heredity
Zsuzsanna Elek, Eszter Losoncz, Katalin Maricza, Zoltan Fuelep, Zsofia Banlaki, Reka Kovacs-Nagy, Gergely Keszler, Zsolt Ronai
Summary: This study found that there are certain genetic variants associated with vWF and ADAMTS13 genes in COVID-19 patients, but no associations were found with disease severity. However, associations with certain clinical parameters were observed. Furthermore, in silico analysis predicted that these variants may lead to conformational alterations in vWF, which could affect its stability and plasma levels.
Article
Medicine, General & Internal
Ingrid Skornova, Tomas Simurda, Jan Stasko, Jana Zolkova, Juraj Sokol, Pavol Holly, Miroslava Dobrotova, Ivana Plamenova, Jan Hudecek, Monika Brunclikova, Alena Stryckova, Peter Kubisz
Summary: von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by defects or deficiency of von Willebrand factor. Laboratory testing for VWF-related disorders requires assessment of VWF levels and activity, as well as multimer analysis to evaluate structural features. The introduction of VWF multimer analysis into standard VWD diagnostics helps in patient classification, treatment selection, and dosage determination.
Article
Engineering, Biomedical
Mansur Zhussupbekov, Rodrigo Mendez Rojano, Wei-Tao Wu, Mehrdad Massoudi, James F. Antaki
Summary: The von Willebrand Factor is a mechano-sensitive protein in the blood that plays a key role in platelet adhesion and aggregation. Its conformational changes from a collapsed to a stretched state regulate its hemostatic function and thrombogenic effect. A continuum model of vWF unfolding was developed within a multi-constituent model of platelet-mediated thrombosis, considering two interconvertible vWF species corresponding to different conformational states. The model was verified in microfluidic systems designed for studying high-shear vWF-mediated thrombosis and von Willebrand Disease screening, showing high concentration of stretched vWF in regions where occlusive thrombosis occurred. The model can be used for numerical simulations in complex geometries, but may face challenges when extending to 3-D arbitrary flows and turbulent flows.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Chemistry, Medicinal
Susan M. M. Shea, Kimberly A. A. Thomas, Rassam M. G. Rassam, Emily P. P. Mihalko, Christina Daniel, Bruce A. A. Sullenger, Philip C. C. Spinella, Shahid M. M. Nimjee
Summary: This study aims to evaluate the inhibitory effect of BB-031 on VWF function and thrombolysis. The results show that BB-031 exhibits dose-dependent responses in different assays and can induce arterial thrombolysis. Additionally, a moderate correlation between VWF function inhibition and thrombolysis is observed.
Review
Hematology
Xue D. Manz, Harm Jan Bogaard, Jurjan Aman
Summary: Increasing evidence suggests that inflammation promotes thrombosis via VWF-mediated mechanisms, and aberrant regulation of VWF is linked to various cardiovascular diseases. Recent insights from clinical diseases provide evidence for direct molecular links between inflammation and thrombosis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Review
Immunology
Leilei Meng, Zichen Song, Anding Liu, Uta Dahmen, Xiao Yang, Haoshu Fang
Summary: Inflammation, driven by the immune response, is a key factor in various diseases. Genetic variations in pivotal immune response genes, particularly SNPs, may affect disease predisposition and clinical outcomes. The LBP gene, which plays a crucial role in inflammation, may be impacted by SNPs and influence infections, inflammatory diseases, metabolic disorders, and cancers.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Hematology
Wolfgang Miesbach, Erik Berntorp
Summary: The limited awareness and challenges in diagnosing and treating patients with von Willebrand disease highlight the need for greater understanding and implementation of long-term prophylactic treatment similar to that used in patients with severe haemophilia.
THROMBOSIS RESEARCH
(2021)
Article
Pathology
Supanun Lauhasurayotin, Chatphatai Moonla, Rungnapa Ittiwut, Chupong Ittiwut, Natsaruth Songthawee, Patcharee Komvilaisak, Rungrote Natesirinilkul, Nongnuch Sirachainan, Ponlapat Rojnuckarin, Darintr Sosothikul, Kanya Suphapeetiporn
Summary: This study conducted whole exome sequencing on Thai patients with type 2 and type 3 VWD, identifying several unique VWF gene mutations that contribute to the phenotypes.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Review
Genetics & Heredity
Marcos Jesse Abrahao Silva, Caroliny Soares Silva, Marcelo Cleyton da Silva Vieira, Pabllo Antonny Silva dos Santos, Cristiane Cunha Frota, Karla Valeria Batista Lima, Luana Nepomuceno Gondim Costa Lima
Summary: This article conducted a systematic review and meta-analysis to investigate the association between a polymorphism of the Toll-like receptor 3 (TLR3) gene and susceptibility to infections. The results showed a significant association between the TLR3 rs3775291 polymorphism and infection risk, particularly with a higher risk in the Asian and American continents.
Article
Hematology
Pamela A. Christopherson, Sandra L. Haberichter, Veronica H. Flood, Ursula O. Sicking, Thomas C. Abshire, Robert R. Montgomery
Summary: This study investigates the diagnosis of Von Willebrand disease (VWD). It finds that a single low VWF:RCo level may be attributed to genetic variants or assay issues, suggesting that using VWF:RCo alone for diagnosis may be insufficient. Repeat testing or using VWF:GPIbM can provide valuable information in establishing a VWD diagnosis.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Genetics & Heredity
Yifei Li, Xinzhuang Shen, Xiaowen Yang, Fuming Lian, Yanping Li, Jinmeng Li, Yongming Huang, Wenzhi Shen, Huan Liu
Summary: CHDH is a transmembrane protein located in mitochondria that is involved in the oxidation of choline to betaine and mitochondrial autophagy. Recent studies have found that CHDH is closely associated with the pathogenesis of various diseases, including tumor prognosis. This article summarizes the genomic localization, protein structure, and basic functions of CHDH, and discusses its progress in research on metabolic disorders and other diseases. In addition, it describes the regulatory role of CHDH in the progression of different types of malignant tumors, potentially through single nucleotide polymorphism (SNP). The study evaluates the feasibility of CHDH as a molecular marker for the diagnosis of metabolic disorders and tumors, providing new targets for the treatment of related diseases.
FRONTIERS IN GENETICS
(2023)
Review
Food Science & Technology
Christina Holzapfel, Melanie Waldenberger, Stefan Lorkowski, Hannelore Daniel
Summary: This article summarizes the evidence for the impact of genetic and epigenetic factors on diseases such as obesity, metabolic syndrome, and diabetes, and evaluates the effectiveness of genotype-based nutrition advice. The study finds that there is generally a lack of evidence for the success of gene-based dietary recommendations, suggesting the need for future personalized nutrition solutions to incorporate more phenotypic measures and individualized tools.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Medicine, General & Internal
Xuebing Chen, Hao Zhang, Shimei Ou, Huijuan Chen
Summary: This study investigated the association between single nucleotide polymorphisms in the 3' UTR sequences of HBV-infected patients and the development and metastasis of hepatocellular carcinoma. A specific SNP in the von Hippel-Lindau gene was found to be associated with HCC occurrence and metastasis. The study suggests that Von Hippel-Lindau rs1642742 contributes to the susceptibility to developing HCC and correlated with tumor metastasis.
Article
Biochemistry & Molecular Biology
Elena Barbon, Charlotte Kawecki, Solenne Marmier, Aboud Sakkal, Fanny Collaud, Severine Charles, Giuseppe Ronzitti, Caterina Casari, Olivier D. Christophe, Cecile V. Denis, Peter J. Lenting, Federico Mingozzi
Summary: Von Willebrand disease (VWD), the most common inherited bleeding disorder, has limited efficacy with current liver-directed gene therapy. This study developed a gene therapy strategy using an optimized AAV vector and endothelial-targeting peptide to deliver the VWF gene into endothelial cells, achieving long-term expression.
Article
Cardiac & Cardiovascular Systems
Jeremy Lagrange, Morel E. Worou, Jean-Baptiste Michel, Alexandre Raoul, Melusine Didelot, Vincent Muczynski, Paulette Legendre, Francois Plenat, Guillaume Gauchotte, Marc-Damien Lourenco-Rodrigues, Olivier D. Christophe, Peter J. Lenting, Patrick Lacolley, Cecile Denis, Veronique Regnault
Summary: VWF induces VSMC proliferation through A2 domain binding to LRP4 receptor and integrin alpha(v)beta(3) signaling. These findings provide new insights into the mechanisms that drive physiological repair and pathological hyperplasia of the arterial vessel wall.
CARDIOVASCULAR RESEARCH
(2022)
Article
Hematology
Elsa P. Bianchini, Mahita Razanakolona, Julie Helms, Fouzia Zouiti, Amelie Couteau-Chardon, Viviana Marin-Esteban, Luc de Chaisemartin, Allan De-Carvalho, Roselyne Bironien, Sylvie Chollet-Martin, Cecile Denis, Jean-Luc Diehl, Marc Vasse, Ferhat Meziani, Delphine Borgel
Summary: The study assessed plasma ZPI antigen levels in patients with septic shock, finding a significant elevation in ZPI concentration in patients compared to healthy controls, regardless of DIC presence. Experimental evidence revealed the involvement of NE in ZPI inactivation during sepsis, proposing a novel mechanism for the procoagulant activity of NETs in immunothrombosis.
THROMBOSIS AND HAEMOSTASIS
(2022)
Editorial Material
Hematology
Cecile V. Denis, Peter J. Lenting
Article
Hematology
Caterina Casari, Remi Favier, Paulette Legendre, Alexandre Kauskot, Frederic Adam, Veronique Picard, Peter J. Lenting, Cecile Denis, Valerie Proulle
Summary: This report describes the successful treatment of splenic injury in a patient with p.V1316M-associated VWD2B and chronic thrombocytopenia using nonoperative management and a combination of VWF replacement therapy and platelet transfusions relayed by TPO-RA.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2022)
Article
Hematology
Claire Kizlik-Masson, Ivan Peyron, Stephane Gangnard, Gaelle Le Goff, Solen M. Lenoir, Sandra Damodaran, Marie Clavel, Stephanie Roullet, Veronique Regnault, Antoine Rauch, Flavien Vincent, Emmanuelle Jeanpierre, Annabelle Dupont, Catherine Ternisien, Thibault Donnet, Olivier D. Christophe, Eric van Belle, Cecile Denis, Caterina Casari, Sophie Susen, Peter J. Lenting
Summary: A nanobody (KB-VWF-D3.1) is identified to distinguish proteolyzed and non-proteolyzed VWF and monitor VWF degradation levels. Reduced intact-VWF levels are observed in patients with von Willebrand disease, aortic stenosis, and patients receiving mechanical circulatory support.
Article
Hematology
Stephanie Roullet, Norman Luc, Julie Rayes, Jean Solarz, Dante Disharoon, Andrew Ditto, Emily Gahagan, Christa Pawlowski, Thibaud Sefiane, Frederic Adam, Caterina Casari, Olivier D. Christophe, Michael Bruckman, Peter J. Lenting, Anirban Sen Gupta, Cecile Denis
Summary: The lack of innovation in von Willebrand disease (VWD) is due to the complexity and heterogeneity of the disease and a lack of recognition of the impact of bleeding symptoms experienced by patients. This study proposes a new approach using synthetic platelet (SP) nanoparticles for the treatment of VWD-2B and severe VWD. The results show that SP can improve thrombus formation and reduce blood loss in VWD-2B and VWF-KO mice.
Article
Cardiac & Cardiovascular Systems
Antoine Rauch, Annabelle Dupont, Mickael Rosa, Maximilien Desvages, Christina Le Tanno, Johan Abdoul, Melusine Didelot, Alexandre Ung, Richard Ruez, Emmanuelle Jeanpierre, Melanie Daniel, Delphine Corseaux, Hugues Spillemaeker, Julien Labreuche, Benedicte Pradines, Natacha Rousse, Peter J. Lenting, Mouhamed D. Moussa, Andre Vincentelli, Jean-Claude Bordet, Bart Staels, Flavien Vincent, Cecile V. Denis, Eric Van Belle, Caterina Casari, Sophie Susen
Summary: Thrombocytopenia is consistently observed in ECMO patients, with a time-dependent decrease in platelet count, GP Ib alpha shedding, and increased soluble GP Ib alpha levels. Shedding of GP Ib alpha is dependent on rheological conditions, with higher rates at high-flow speeds.
CIRCULATION RESEARCH
(2023)
Article
Hematology
Alexis Texier, Peter J. Lenting, Cecile Denis, Stephanie Roullet, Olivier D. Christophe
Summary: This study reveals the binding between von Willebrand factor and angiopoietin-2, with angiopoietin-2 enhancing the binding of von Willebrand factor to angiopoietin-1.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Alexandre Kauskot, Coralie Mallebranche, Arnaud Bruneel, Francois Fenaille, Jean Solarz, Toscane Viellard, Miao Feng, Christelle Reperant, Jean-Claude Bordet, Sophie Cholet, Cecile Denis, Genevieve McCluskey, Sylvain Latour, Emmanuel Martin, Isabelle Pellier, Dominique Lasne, Delphine Borgel, Sven Kracker, Alban Ziegler, Marie Tuffigo, Benjamin Fournier, Charline Miot, Frederic Adam
Summary: XMEN disease, caused by loss-of-function mutations in the MAGT1 gene, is associated with platelet dysfunction and defective N-glycosylation, which may explain the bleeding events in patients with XMEN disease.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Melissa Bou-Jaoudeh, Angelina Mimoun, Sandrine Delignat, Ivan Peyron, Ladislas Capdevila, Victoria Daventure, Claire Deligne, Jordan D. Dimitrov, Olivier D. Christophe, Cecile V. Denis, Peter J. Lenting, Valerie Proulle, Sebastien Lacroix-Desmazes
Summary: This study investigated the impact of IdeS treatment in inhibitor-positive HA mice injected with emicizumab. The results showed that IdeS efficiently eliminated anti-FVIII IgG and restored the hemostatic efficacy of exogenous FVIII, unaffected by the presence of emicizumab and polyclonal human IgG in the mice.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Marie-Daniela Dubois, Ivan Peyron, Olivier-Nicolas Pierre-Louis, Serge Pierre-Louis, Johalene Rabout, Pierre Boisseau, Annika de Jong, Sophie Susen, Jenny Goudemand, Remi Neviere, Pascal Fuseau, Olivier D. Christophe, Peter J. Lenting, Cecile Denis, Caterina Casari
Summary: This study reports two mutations in the D4 domain of VWF that induce combined qualitative and quantitative defects. One mutation leads to almost complete intracellular retention of the protein, while the other mutation results in reduced binding to collagen and platelet receptors.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)