Article
Biochemistry & Molecular Biology
Chao Han, Pengxuan Ren, Medina Mamtimin, Linus Kruk, Edita Sarukhanyan, Chenyu Li, Hans-Joachim Anders, Thomas Dandekar, Irena Krueger, Margitta Elvers, Silvia Goebel, Kristin Adler, Goetz Muench, Thomas Gudermann, Attila Braun, Elmina Mammadova-Bach
Summary: This study analyzed the collagen- and CRP-binding surfaces of GPVI monomers and dimers using computational modeling and bioinformatics, and compared them with other mammalian GPVI isoforms. Experimental results show that the EA-20 antibody inhibits platelet adhesion and aggregation in response to collagen and CRP, but not to fibrin, and prevents thrombus formation in whole blood. Therefore, the blockade of this minimal collagen-binding epitope of GPVI with the EA-20 antibody could represent a new anti-thrombotic approach.
Article
Hematology
Julia S. Gauer, Cedric Duval, Rui-Gang Xu, Fraser L. Macrae, Helen R. McPherson, Christian Tiede, Darren Tomlinson, Steve P. Watson, Robert A. S. Ariens
Summary: The interaction between GPVI and fibrin significantly affects the formation of procoagulant platelets and the structure of blood clots. Inhibition of GPVI signaling increases clot porosity and impairs clot contractibility to varying degrees.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Raluca A. Neagoe, Elizabeth E. Gardiner, David Stegner, Bernhard Nieswandt, Steve P. Watson, Natalie S. Poulter
Summary: The study reveals the importance of Rac1 in the activation of human and murine platelets in response to GPVI ligands, although the mode of action differs between the two species.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Annalena Fink, Anne-Katrin Rohlfing, Valerie Dicenta, David Schaale, Marcel Kremser, Zoi Laspa, Manuel Sigle, Xiaoqing Fu, Andreas Pelzer, Melina Fischer, Patrick Muenzer, Tatsiana Castor, Karin Anne Lydia Mueller, Oliver Borst, Michael Laemmerhofer, Meinrad Paul Gawaz
Summary: In this study, we found that hemin strongly enhances platelet activation, aggregation, and aggregate formation on immobilized collagen. The hemin-induced decrease in surface expression of GPVI is independent of platelet aggregation. We also discovered that the proprotein convertase furin controls hemin-induced GPVI degradation and platelet function.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Henrike Hoermann, Irena Krueger, Nadine Maurus, Friedrich Reusswig, Yi Sun, Christina Kohlmorgen, Maria Grandoch, Jens W. Fischer, Margitta Elvers
Summary: Biglycan plays a crucial role in hemostasis and thrombosis by binding and activating platelets through GPVI. Deficiency of biglycan results in reduced platelet adhesion to injured vessels and prolonged bleeding times.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Jeffrey Miles, S. Lawrence Bailey, Ava M. Obenaus, Molly Y. Mollica, Chomkan Usaneerungrueng, Daire Byrne, Lydia Fang, Jake R. Flynn, Jill Corson, Barbara Osborne, Katie Houck, Yi Wang, Yu Shen, Xiaoyun Fu, Jing-Fei Dong, Nathan J. Sniadecki, Moritz Stolla
Summary: The study compared the function of cold-stored platelets with room temperature-stored platelets and found that cold-stored platelets formed larger aggregates under shear, but had reduced GPVI levels. After transfusion into humans, cold-stored platelets showed lower aggregation rates in response to collagen. In a mouse model, platelets stored in cold had lower response rates to GPVI agonist and lower GPVI levels post-transfusion. The data supports short-lived benefits of cold storage and calls for further investigations into cold-stored platelets.
Article
Hematology
Alexandre Slater, Ying Di, Joanne C. Clark, Natalie J. Jooss, Eleyna M. Martin, Fawaz Alenazy, Mark R. Thomas, Robert A. S. Ariens, Andrew B. Herr, Natalie S. Poulter, Jonas Emsley, Steve P. Watson
Summary: The research found that the nanobody Nb2 against GPVI can effectively inhibit collagen-induced platelet aggregation, showing strong binding ability and low KD value. The binding epitope of Nb2 is located adjacent to the collagen-related peptide binding groove in the D1 domain. Additionally, a novel conformation of GPVI involving a domain swap between the D2 domains was observed.
Article
Nanoscience & Nanotechnology
Jyotsna Kailashiya, Debabrata Dash
Summary: This study found that nanoceria particles have effects on human platelet function and blood coagulation, including reducing platelet aggregation and secretion of granule contents, as well as impairing fibrin polymerization and thrombus retraction. Furthermore, nanoceria may cause early clot formation in whole blood. These findings highlight the need for re-evaluation and careful planning of biomedical applications of nanoceria.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Review
Pharmacology & Pharmacy
Xiaowei Wang, Melanie Ziegler, James D. McFadyen, Karlheinz Peter
Summary: Molecular imaging is a rapidly advancing field that offers improved understanding of thrombotic diseases and the exciting prospect of earlier diagnosis and individualized therapy through better disease markers, contrast agents, and scanner technologies.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Hematology
Joanne C. Clark, Raluca A. I. Neagoe, Malou Zuidscherwoude, Deirdre M. Kavanagh, Alexandre Slater, Eleyna M. Martin, Mark Soave, David Stegner, Bernhard Nieswandt, Natalie S. Poulter, Johan Hummert, Dirk-Peter Herten, Michael G. Tomlinson, Stephen J. Hill, Steve P. Watson
Summary: The study found that GPVI is expressed as a mixture of monomers and dimers, and dimerization through the D2 domain is not critical for activation. Using FRET, it was shown that endogenous GPVI is expressed at least partially as a dimer on resting and activated platelet membranes.
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Rui-Gang Xu, Julia S. Gauer, Stephen R. Baker, Alexandre Slater, Eleyna M. Martin, Helen R. McPherson, Cedric Duval, Iain W. Manfield, Arkadiusz M. Bonna, Steve P. Watson, Robert A. S. Ariens
Summary: The study demonstrates that dimeric GPVI binds to fibrinogen with higher affinity compared to the monomer, primarily through avidity effects. The interaction of GPVI with the α C-region of fibrinogen is crucial for its binding. These findings suggest that clustering of GPVI through the α C-region during fibrin polymerization may lead to downstream signaling, platelet activation, and clot growth.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Izmarie Poventud-Fuentes, Keon Woo Kwon, Jeongyun Seo, Maurizio Tomaiuolo, Timothy J. Stalker, Lawrence F. Brass, Dongeun Huh
Summary: This paper presents a microengineering approach for in vitro modeling of hemostasis, replicating key features of human blood vessels and evaluating the effects of anticoagulants and antiplatelet agents. This vascular injury-on-a-chip system could serve as a platform for preclinical investigation of hematological disorders and emerging therapeutic approaches.
Article
Cell Biology
Marie-Astrid van Dievoet, Davide Brusa, Marie Octave, Sandrine Horman, Xavier Stephenne
Summary: This article describes an activation problem encountered with anti-GPVI, clone HY101, in a whole blood multicolor flow cytometry panel. Platelet activation was observed after the addition of anti-GPVI, as indicated by increased expression of activation markers CD62P, PAC-1, CD63, and CD107a. This finding was further confirmed by platelet aggregation studies.
Review
Hematology
James I. Hearn, Elizabeth E. Gardiner
Summary: This article discusses the role of platelets in the formation of a hemostatic response and vascular injury repair, as well as their function in flowing blood. The article highlights the importance of platelet adhesion and activation in forming and strengthening adhesive ties, and discusses the challenges faced in research.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Hematology
Rainer Kaiser, Raphael Escaig, Jan Kranich, Marie-Louise Hoffknecht, Afra Anjum, Vivien Polewka, Magdalena Mader, Wenbo Hu, Larissa Belz, Christoph Gold, Anna Titova, Michael Lorenz, Kami Pekayvaz, Stefan Kaab, Florian Gaertner, Konstantin Stark, Thomas Brocker, Steffen Massberg, Leo Nicolai
Summary: Impairment of vascular integrity is a characteristic of inflammatory diseases. This study demonstrates the essential role of procoagulant platelets in preventing inflammatory bleeding by promoting coagulation cascade activation. The presence of exposed collagen triggers platelet arrest and subsequent procoagulant activation. The findings highlight the importance of procoagulant platelets in maintaining vascular integrity during inflammation.
Article
Biochemistry & Molecular Biology
Maan H. Harbi, Christopher W. Smith, Fawaz O. Alenazy, Phillip L. R. Nicolson, Alok Tiwari, Steve P. Watson, Mark R. Thomas
Summary: The study investigates the effect of Syk inhibitor fostamatinib as an antiplatelet drug, showing that it mildly inhibits platelet responses induced by atherosclerotic plaque and that this effect is amplified by aspirin and ticagrelor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Ana Bura, Maria Antonietta de Matteis, Markus Bender, Maurice Swinkels, Jurjen Versluis, A. J. Gerard Jansen, Antonija Jurak Begonja
Summary: Lowe syndrome is a rare disorder that affects the brain, eyes, and kidneys. It is caused by mutations in the OCRL protein. Some patients with Lowe syndrome have bleeding disorders and impaired platelet function. Experiments show that OCRL inhibition affects cytoskeletal rearrangement in platelet activation, which may explain the mild bleeding problems in patients with Lowe syndrome.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Alexandra Mazharian, Blandine Maitre, Alicia Bornert, Desline Hennequin, Marc Lourenco-Rodrigues, Mitchell J. Geer, Christopher W. Smith, Silke Heising, Michaela Walter, Florian Montel, Lucy S. K. Walker, Henri de la Salle, Steve P. Watson, Christian Gachet, Yotis A. Senis
Summary: Mice lacking the G6b-B receptor exhibit a range of platelet abnormalities, including macrothrombocytopenia and reduced collagen receptor expression. Treatment with romiplostim, a thrombopoietin mimetic, showed promising results in rescuing platelet counts and function in G6b KO mice. However, inhibitors targeting Syk and Src kinases had limited effects on platelet abnormalities. These findings suggest that romiplostim may be a potential therapeutic option for patients lacking functional G6b-B.
Article
Hematology
Philippe Billiald, Alexandre Slater, Martin Welin, Joanne C. Clark, Stephane Loyau, Martine Pugniere, Isabella G. Jiacomini, Nadia Rose, Kristell Lebozec, Elie Toledano, Deborah Francois, Steve P. Watson, Martine Jandrot-Perrus
Summary: This study shows that glenzocimab, a humanized antibody fragment, blocks the binding of GPVI to vascular collagen and fibrin through steric hindrance and structural change. This finding is significant for the development of new antiplatelet molecules with a low bleeding risk.
Article
Cell Biology
Markus Spindler, Kristina Mott, Harald Schulze, Markus Bender
Summary: We demonstrate a simple and rapid method to enrich mature megakaryocytes (MKs) from murine adult bone marrow by size exclusion. Reanalysis of the isolated MKs confirmed the expression of MK and platelet-specific surface receptors, as well as a clear enrichment of MK-specific proteins/transcripts. This protocol serves as a compatible addition to established isolation methods.
Article
Hematology
Asim Cengiz Akbulut, Ryanne A. Arisz, Constance C. F. M. J. Baaten, Gaukhar Baidildinova, Aarazo Barakzie, Rupert Bauersachs, Jur Ten Berg, Wout W. A. van den Broek, H. C. de Boer, Amandine Bonifay, Vanessa Broker, Richard J. Buka, Hugo ten Cate, Arina J. ten Cate-Hoek, S. Cointe, Ciro De Luca, Ilaria De Simone, Rocio Vacik Diaz, Francoise Dignat-George, Kathleen Freson, Giulia Gazzaniga, Eric C. M. van Gorp, Anxhela Habibi, Yvonne M. C. Henskens, Aaron F. J. Iding, Abdullah Khan, Gijsje H. Koenderink, Akhil Konkoth, Romaric Lacroix, Trisha Lahiri, Wilbur Lam, Rachel E. Lamerton, Roberto Lorusso, Qi Luo, Coen Maas, Owen J. T. McCarty, Paola E. J. van der Meijden, Joost C. M. Meijers, Adarsh K. Mohapatra, Neta Nevo, Alejandro Pallares Robles, Philippe Poncelet, Christoph Reinhardt, Wolfram Ruf, Ronald Saraswat, Claudia Schonichen, Roger Schutgens, Paolo Simioni, Stefano Spada, Henri M. H. Spronk, Karlygash Tazhibayeva, Jecko Thachil, Rocio Vacik Diaz, L. Vallier, Alicia Veninga, Peter Verhamme, Chantal Visser, Steve P. Watson, Philip Wenzel, Ruth A. L. Willems, Anne Willers, Pengyu Zhang, Konstantinos Zifkos, Anton Jan van Zonneveld
Summary: The Fourth Maastricht Consensus Conference on Thrombosis covered a wide range of topics, including the role of coagulation proteins in cardiovascular disease, novel mechanisms of thrombosis, strategies to limit bleeding risks, hemostasis in extracorporeal systems, and clinical dilemmas in thrombosis and antithrombotic management. The conference also revisited the coagulopathy associated with COVID-19.
THROMBOSIS AND HAEMOSTASIS
(2023)
Letter
Hematology
Helena C. Brown, Sarah Beck, Stefano Navarro, Ying Di, Eva M. Soriano Jerez, Jana Kaczmarzyk, Steven G. Thomas, Valbona Mirakaj, Steve P. Watson, Bernhard Nieswandt, David Stegner
Article
Biology
Joanne C. Clark, Eleyna M. Martin, Luis A. Moran, Ying Di, Xueqing Wang, Malou Zuidscherwoude, Helena C. Brown, Deirdre M. Kavanagh, Johan Hummert, Johannes A. Eble, Bernhard Nieswandt, David Stegner, Alice Y. Pollitt, Dirk-Peter Herten, Michael G. Tomlinson, Angel Garcia, Steve P. Watson
Summary: Fluorescence correlation spectroscopy was used to investigate the clustering of CLEC-2 induced by crosslinked nanobody ligands. The results showed that the valency of the ligands and the expression levels of CLEC-2 were important factors in determining the activation of CLEC-2. Divalent ligands were found to be partial agonists while tetravalent ligands stimulated platelet aggregation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Hematology
Claudia Schoenichen, Samantha J. Montague, Sanne L. N. Brouns, James J. Burston, Judith M. E. M. Cosemans, Kerstin Jurk, Beate E. Kehrel, Rory R. Koenen, Fionnuala Ni Ainle, Valerie B. O'Donnell, Oliver Soehnlein, Steve P. Watson, Marijke J. E. Kuijpers, Johan W. M. Heemskerk, Magdolna Nagy
Summary: This study reveals the key interaction mechanisms between platelets and neutrophils in arterial thrombus formation. Activated platelet integrin αIIbβ3 plays a role in preventing leukocyte adhesion, while platelet-released substances promote neutrophil activation. These findings provide insights for potential pharmacological intervention.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Editorial Material
Pharmacology & Pharmacy
Joanne C. Clark, Steve P. Watson, Dylan M. Owen
Summary: This article discusses how a combination of agent-based modelling, advanced microscopy, and structural studies can provide new insights into the regulation of clustering, including spatial considerations, and reveal novel targets for therapeutic intervention.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Hematology
Foteini-Nafsika Damaskinaki, Natalie J. Jooss, Eleyna M. Martin, Joanne C. Clark, Mark R. Thomas, Natalie S. Poulter, Jonas Emsley, Barrie Kellam, Steve P. Watson, Alexandre Slater
Summary: This study investigates the binding sites of three high-affinity nanobodies, Nb2, Nb21, and Nb35, on the platelet-signaling receptor GPVI. The researchers found that all three nanobodies can bind to the D1 domain of GPVI and inhibit collagen-induced GPVI signaling. They also identified common target residues, Arg46, Tyr47, and Ala57, on GPVI for these nanobodies. Additionally, the study negates the idea that GPVI dimerization induces a conformational change required for ligand binding.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Julia S. Gauer, Cedric Duval, Rui-Gang Xu, Fraser L. Macrae, Helen R. McPherson, Christian Tiede, Darren Tomlinson, Steve P. Watson, Robert A. S. Ariens
Summary: The interaction between GPVI and fibrin significantly affects the formation of procoagulant platelets and the structure of blood clots. Inhibition of GPVI signaling increases clot porosity and impairs clot contractibility to varying degrees.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Caroline Kardeby, Alice Evans, Joana Campos, Afraa Moosa Al-Wahaibi, Christopher W. Smith, Alexandre Slater, Eleyna M. Martin, Sonia Severin, Alexander Brill, Gunnar Pejler, Yi Sun, Steve P. Watson
Summary: English Summary: The study identified PEAR1 as a receptor for heparin and HPGM, and PI3K(3 as a key signaling molecule downstream of PEAR1 in platelets. These findings may provide important insights into the role of PEAR1 in cardiovascular disease.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Fawaz O. Alenazy, Maan H. Harbi, Dean P. Kavanagh, Joshua Price, Paul Brady, Oscar Hargreaves, Paul Harrison, Alexandre Slater, Alok Tiwari, Phillip L. R. Nicolson, Derek L. Connolly, Paulus Kirchhof, Neena Kalia, Martine Jandrot-Perrus, Pierre H. Mangin, Steve P. Watson, Mark R. Thomas
Summary: This study investigated the additional antithrombotic effects of combining glenzocimab, a GPVI inhibitor, with aspirin and ticagrelor. The results showed that glenzocimab enhanced platelet inhibition and reduced atherosclerotic plaque-induced platelet aggregation, adhesion, and activation. Compared to a GPIIb/IIIa inhibitor, glenzocimab exhibited similar antithrombotic effects but with less inhibition of general hemostasis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)