Article
Pharmacology & Pharmacy
Lauren G. Poole, Anna-Katherine Fournier, Holly M. Cline-Fedewa, Anna K. Kopec, James P. Luyendyk, Dafna J. Groeneveld
Summary: VWF plays different roles in experimental acute and chronic ANIT-induced cholestatic liver injury.
Article
Hematology
Maurice Swinkels, Sophie Hordijk, Petra E. Buergisser, Johan A. Slotman, Tom Carter, Frank W. G. Leebeek, A. J. Gerard Jansen, Jan Voorberg, Ruben Bierings
Summary: This study investigated the release of VWF and VWFpp from individual alpha-granules in response to different physiological stimuli. The results showed that the secretion of alpha-granule cargo increased in a dose-dependent manner upon activation of PAR-1 and GPVI signaling pathways. However, there were differential release patterns for VWF and VWFpp.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Engineering, Biomedical
Noel G. Tsyu, Aleksey V. Belyaev
Summary: A multi-subunit glycoprotein called Von Willebrand factor (VWF) in blood plasma is responsible for mediating platelet adhesion to damaged blood vessel walls. The adhesion of VWF to collagen is crucial for platelet hemostasis and thrombosis, acting as a molecular bridge between injury and platelet adhesion receptors. This study proposes a simulation framework for VWF-mediated platelet adhesion under the influence of shear flow, using particles representing VWF multimers and platelets immersed in a viscous fluid. The model considers the flattened platelet shape and balances detail of description with computational complexity.
INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING
(2023)
Article
Hematology
Nikolett Wohner, Silvie Sebastian, Vincent Muczynski, Dana Huskens, Bas de Laat, Philip G. de Groot, Peter J. Lenting
Summary: The study reveals that VWF strings secreted from endothelial cells are only partially covered with platelets, and osteoprotegerin plays a role in regulating platelet adhesion to VWF. This regulatory mechanism may be more relevant under inflammatory conditions.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Hematology
Dafna J. Groeneveld, Lauren G. Poole, James P. Luyendyk
Summary: Liver disease is associated with significant changes in the hemostatic system, with anticoagulants showing promise in slowing disease progression but also posing bleeding risks. Elevated levels of VWF may accelerate intrahepatic thrombosis, suggesting a potential link between VWF function and the progression of liver disease.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Nicholas A. Arce, Yi Liu, Wenchun Chen, X. Frank Zhang, Renhao Li
Summary: This study aimed to determine and characterize the autoinhibitory properties of mouse VWF. The results showed that recombinant mouse AIM-A1 binds with higher affinity to GPIb alpha than its human counterpart. Activated A1 fragments lacking the AIM can effectively agglutinate platelets across the species barrier. The unfolding force of mouse AIM was found to be similar to the human AIM. These findings suggest that the regulation of VWF-GPIb alpha binding has been specifically tuned to work optimally in different rheological architectures, potentially due to differences in the AIM sequence.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Johana Hrdinova, Delia I. Fernandez, Bogac Ercig, Bibian M. E. Tullemans, Dennis P. L. Suylen, Stijn M. Agten, Kerstin Jurk, Tilman M. Hackeng, Karen Vanhoorelbeke, Jan Voorberg, Chris P. M. Reutelingsperger, Kanin Wichapong, Johan W. M. Heemskerk, Gerry A. F. Nicolaes
Summary: This study designed and synthesized stable cyclic peptides to interfere with the interaction between VWF A1 domain and GPIb alpha. The selected peptides showed low binding free energy and retained their interference in the binding of VWF to GPIb-V-IX, as confirmed by flow cytometry. These peptides phenotypically mimicked the changes seen with the anti-VWF A1 domain antibody CLB-RAg35, although they were less potent. The improved peptide opt-mono-ORbIT demonstrated increased inhibitory activity under flow.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Cell Biology
Valentino Le Noci, Giancarla Bernardo, Francesca Bianchi, Elda Tagliabue, Michele Sommariva, Lucia Sfondrini
Summary: The microbiota is a complex ecosystem of active microorganisms in mammals, playing critical roles in maintaining health, symbiosis with the immune system, pathogen defense, and tolerance to commensal microbes. Toll-like receptors (TLRs) are key in sensing the microbiota, associated with cancer development, and potentially disrupting TLR tolerance.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Mengchen Yang, Katie L. Houck, Xinlong Dong, Maria Hernandez, Yi Wang, Sriram S. Nathan, Xiaoping Wu, Vahid Afshar-Kharghan, Xiaoyun Fu, Miguel A. Cruz, Jianning Zhang, Angelo Nascimbene, Jing-fei Dong
Summary: Enhanced VWF adhesion in LVAD patients induces platelet microvesiculation and activates endothelial cells, leading to vascular permeability and angiogenesis in a VWF-dependent manner.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Ling Wei, Xue-Sen Wen, Cory J. Xian
Summary: Chemotherapy-induced intestinal mucositis is a painful condition that affects a significant number of patients undergoing chemotherapy. Recent research has highlighted the relationship between dysbiosis of intestinal microbiota and mucositis, showing that chemotherapy can shape the microbiota and worsen mucositis through TLR signaling pathways. This review aims to explore how gut microbiota affects the pathogenesis of mucositis and provide potential new strategies for treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Francesco Barilla, Vittoria Cammisotto, Simona Bartimoccia, Lorenzo Loffredo, Cristina Nocella, Noemi Bruno, Concetta Torromeo, Paolo Rosa, Nicola Viceconte, Pasquale Pignatelli, Carlo Gaudio, Roberto Carnevale, Francesco Violi
Summary: This study provides evidence that platelet toll-like receptor 4 (TLR4) is activated in patients with myocardial infarction (MI) and suggests circulating lipopolysaccharides (LPS) as a potential trigger.
THROMBOSIS RESEARCH
(2022)
Article
Hematology
Maurice Swinkels, Ferdows Atiq, Petra E. Burgisser, Johan A. Slotman, Adriaan B. Houtsmuller, Cilia de Heus, Judith Klumperman, Frank W. G. Leebeek, Jan Voorberg, Arend Jan Gerard Jansen, Ruben Bierings
Summary: The study used structured illumination microscopy (SIM) to analyze the VWF content and organization in platelets of healthy individuals and patients with VWD. It revealed different changes in the alpha-granule compartment of platelets in VWD patients, allowing stratification of patients with different VWF defects.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2021)
Review
Immunology
Ling Ji, Siyuan Hao, Jiantao Wang, Jing Zou, Yan Wang
Summary: Radiotherapy and/or chemotherapy-induced oral mucositis (RIOM/CIOM) is a common complication in cancer patients. TLRs have a significant role in RIOM/CIOM and may serve as a novel mechanism for therapeutic interventions.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Margaret R. Connolly, Kasinath Kuravi, Lars Burdorf, Lori Sorrells, Benson Morrill, Arielle Cimeno, Todd Vaught, Amy Dandro, Selin Sendil, Zahra A. Habibabady, Jeffery Monahan, Tiezheng Li, John LaMattina, Willard Eyestone, David Ayares, Carol Phelps, Agnes M. Azimzadeh, Richard N. Pierson
Summary: Research has shown that implanting humanized von Willebrand factor (pvWF) from pigs into pig organs can reduce thrombocytopenia and platelet activation that may occur during xenotransplantation.
XENOTRANSPLANTATION
(2021)
Article
Biochemistry & Molecular Biology
Johana Hrdinova, Delia I. Fernandez, Bogac Ercig, Bibian M. E. Tullemans, Dennis P. L. Suylen, Stijn M. Agten, Kerstin Jurk, Tilman M. Hackeng, Karen Vanhoorelbeke, Jan Voorberg, Chris P. M. Reutelingsperger, Kanin Wichapong, Johan W. M. Heemskerk, Gerry A. F. Nicolaes
Summary: This study designed and synthesized stable cyclic peptides to interfere with the interaction between VWF A1 domain and GPIb alpha. The selected peptides showed low binding free energy and retained their interference in the binding of VWF to GPIb-V-IX, as confirmed by flow cytometry. These peptides phenotypically mimicked the changes seen with the anti-VWF A1 domain antibody CLB-RAg35, although they were less potent. The improved peptide opt-mono-ORbIT demonstrated increased inhibitory activity under flow.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Hematology
Kerstin Jurk
THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Biochemistry & Molecular Biology
Nadja Paeslack, Maximilian Mimmler, Stefanie Becker, Zhenling Gao, My Phung Khuu, Amrit Mann, Frano Malinarich, Tommy Regen, Christoph Reinhardt
Summary: Gut commensals play a significant role in the modulation of tryptophan metabolism, affecting innate immune cell functions and promoting the production of specific cells and cytokines. Microbiota-derived tryptophan metabolites also influence vascular endothelium and can impact the development of vascular inflammatory phenotypes.
Editorial Material
Biochemistry & Molecular Biology
Marijke J. E. Kuijpers, Johan W. M. Heemskerk, Kerstin Jurk
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Paul Stamm, Sanela Kalinovic, Matthias Oelze, Sebastian Steven, Alexander Czarnowski, Miroslava Kvandova, Franziska Bayer, Christoph Reinhardt, Thomas Muenzel, Andreas Daiber
Summary: The prevalence and clinical importance of arterial hypertension continue to increase. Inorganic nitrite (NO2-) is an attractive dietary antihypertensive agent, but its metabolism and mode of action are not fully understood. This study found that the loss of vasodilatory potency in response to oxidants was more pronounced for acetylcholine (ACh) compared to nitrite ex vivo. The gastrointestinal microbiome appears to play a key role in nitrite metabolism and bioactivation.
Article
Biochemistry & Molecular Biology
Anja Eckelt, Franziska Wichmann, Franziska Bayer, John Eckelt, Jonathan Gross, Till Opatz, Kerstin Jurk, Christoph Reinhardt, Klytaimnistra Kiouptsi
Summary: The study compared the effects of an ethyl hydroxyethyl cellulose (EHEC) solution with other biocompatible materials on platelet aggregation. The results showed that the EHEC solution exhibited shear-thinning behavior similar to human blood and did not enhance blood clot formation or platelet aggregation and activation, suggesting its potential as a biocompatible carrier material in blood circulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Kerstin Jurk, Anke Adenaeuer, Stefanie Sollfrank, Kathrin Gross, Friederike Haeuser, Andreas Czwalinna, Josef Erkel, Nele Fritsch, Dana Marandiuc, Martin Schaller, Karl J. Lackner, Heidi Rossmann, Frauke Bergmann
Summary: In this study, a novel GATA1 missense variant was detected in a male patient and his daughter, causing moderate bleeding diathesis and platelet abnormalities. The dysfunction of GATA1 also had mild effects on erythrocytes. Additionally, a mild SLC4A1 defect may contribute to spherocytosis and hemolysis in the daughter.
Article
Immunology
Viola Krenzlin, Johannes Schoche, Sarah Walachowski, Christoph Reinhardt, Markus P. Radsak, Markus Bosmann
Summary: Polyphosphates are highly conserved polymers found in all living cells. The administration of long-chain polyphosphates to mice resulted in proinflammatory responses and lung injury. These effects were attenuated after neutrophil depletion. Long-chain polyphosphates were found to modulate cytokine release and immune response in both mouse and human neutrophils. The findings suggest that polyphosphates could be a potential therapeutic target for bacterial infections.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pengyu Zhang, Fiorella A. Solari, Johan W. M. Heemskerk, Marijke J. E. Kuijpers, Albert Sickmann, Ulrich Walter, Kerstin Jurk
Summary: The mechanisms controlling the activities of Btk and Syk in human platelets were investigated in this study. It was found that PKC, PKA and PP2A jointly regulate the activation of Btk induced by GPVI. PKC activation promotes the tyrosine phosphorylation of Btk, while PKA activation suppresses the S180 phosphorylation of Btk and S297 phosphorylation of Syk. PP2A inhibition only increases the S297 phosphorylation of Syk. The study reveals the regulatory mechanisms of GPVI-Syk-Btk signaling pathway in human platelets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Vincent ten Cate, Juergen H. Prochaska, Andreas Schulz, Markus Nagler, Alejandro Pallares Robles, Kerstin Jurk, Thomas Koeck, Steffen Rapp, Christoph Dueber, Thomas Muenzel, Stavros V. Konstantinides, Philipp S. Wild
Summary: This study compared the clinical characteristics and outcomes of isolated pulmonary embolism (PE) and deep vein thrombosis (DVT)-associated PE. It found that isolated PE had different clinical characteristics, with a higher proportion of female patients and higher prevalence of risk factors such as recent invasive surgery, history of myocardial infarction, left-sided heart failure, peripheral artery disease, and diabetes mellitus. In terms of clinical outcomes, isolated PE had a lower risk of recurrent VTE but a higher risk of arterial thrombosis compared to DVT-associated PE.
Article
Hematology
Giulia Pontarollo, Christoph Reinhardt
Summary: In this study, the glycoprotein IIb (GPIIb)/G alpha(13)/Src tyrosine kinase (c-Src)/14-3-3 zeta signaling axis was identified as necessary for platelet migration. The research also sheds light on the mechanism by which the antineoplastic oral tyrosine kinase inhibitor dasatinib increases the risk of inflammation-associated mucosal hemorrhage.
Correction
Endocrinology & Metabolism
Giulia Pontarollo, Bettina Kollar, Amrit Mann, My Phung Khuu, Klytaimnistra Kiouptsi, Franziska Bayer, Ines Brandao, Valeriya V. Zinina, Jennifer Hahlbrock, Frano Malinarich, Maximilian Mimmler, Sudhanshu Bhushan, Federico Marini, Wolfram Ruf, Meriem Belheouane, John F. Baines, Kristina Endres, Scott M. Reba, Verena K. Raker, Carsten Deppermann, Christoph Welsch, Markus Bosmann, Natalia Soshnikova, Benoit Chassaing, Mattias Bergentall, Felix Sommer, Fredrik Backhed, Christoph Reinhardt
Article
Materials Science, Biomaterials
Richard da Costa Marques, Johanna Simon, Cyril D'Arros, Katharina Landfester, Kerstin Jurk, Volker Mailaender
Summary: This study investigated the adsorbed protein composition on calcium phosphate (CaP) surfaces combined with hemoderivatives, and found abundant non-regenerative and anti-angiogenic proteins on the surfaces. The adsorbed pro-angiogenic growth factors were also decreased. Furthermore, the CaP surfaces only stimulated angiogenesis when kept in the hemoderivative medium.
REGENERATIVE BIOMATERIALS
(2022)