Review
Hematology
Gina Perrella, Magdolna Nagy, Steve P. Watson, Johan W. M. Heemskerk
Summary: GPVI is a receptor expressed on megakaryocytes and platelets that plays a role in both arterial and venous thrombus formation, as well as in the formation of platelet-leukocyte complexes. It is emerging as a potential therapeutic target for venous thrombosis, pulmonary thromboembolism, and cancer metastasis due to its involvement in venous thrombus formation and thromboinflammation. Circulating soluble GPVI is also being explored as a biomarker for thrombosis-related complications.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
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
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
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
Biochemistry & Molecular Biology
Shuzhao Chen, Limei Zhang, Lezong Chen, Qianqian Huang, Yun Wang, Yang Liang
Summary: This study comprehensively evaluated the role of platelet-related signaling pathways in various cancers and their responses to immune checkpoint blockade therapy. The results showed that high glycoprotein VI-mediated platelet activation (GMPA) scores were associated with a good prognosis for all 19 types of cancers. The GMPA signature score could serve as an independent prognostic factor for patients with skin cutaneous melanoma (SKCM) and was also linked to tumor immunity. Moreover, the GMPA signature score was a more reliable predictor of the response to anti-PD-1 blockade therapy in metastatic melanoma compared to other signature scores.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Hematology
Shqipdona Lahu, Kristin Adler, Katharina Mayer, Ralph Hein-Rothweiler, Isabell Bernlochner, Gjin Ndrepepa, Stefanie Schuepke, Stefan Holdenrieder, Dario Bongiovanni, Karl-Ludwig Laugwitz, Heribert Schunkert, Meinrad Gawaz, Steffen Massberg, Adnan Kastrati, Gotz Muench
Summary: In patients with chronic coronary syndrome undergoing percutaneous coronary intervention, plasma levels of sGPVI did not correlate with platelet aggregation but patients with higher baseline levels of sGPVI had an increased risk of bleeding at 30 days after PCI.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Pharmacology & Pharmacy
Allan Valenzuela, Miriam Ayuso, Laura Buyssens, Chloe Bars, Chris Van Ginneken, Yann Tessier, Steven Van Cruchten
Summary: This study evaluated the effects of various ASO sequences and modifications on platelets in adult and juvenile Gottingen minipigs. The results were compared to human data and showed remarkable similarities, validating the use of Gottingen minipigs for ASO safety testing. The differential abundance of GPVI and PF4 in minipigs provides insight into ASO-induced thrombocytopenia in pediatric patients.
Article
Hematology
Mahmoud I. Elbadry, Ahmed Tawfeek, Mohammed G. Abdellatif, Eman H. Salama, Ahmed Abudeif, Hany Mahmoud, Mohamed Ezeldin, Rasha Mokhtar Abdelkareem, Usama M. Rashad
Summary: In a study of 145 previously healthy young adults with COVID-19, it was found that occurrence of unexplained thrombotic events was related to thrombophilic genes, coagulation factors, and inflammatory markers. Thrombosis may be associated with specific gene mutations or coagulation abnormalities.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)