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
Pharmacology & Pharmacy
Yulong Li, Guang Xin, Shiyi Li, Yuman Dong, Yuda Zhu, Xiuxian Yu, Chengyu Wan, Fan Li, Zeliang Wei, Yilan Wang, Kun Zhang, Qingqiu Chen, Hai Niu, Wen Huang
Summary: This study reveals the regulatory role of PD-L1 in platelet activation and thrombosis. PD-L1 knockout inhibits platelet activation and thrombus formation, and improves the severity of ischemic stroke and survival rate.
FRONTIERS IN PHARMACOLOGY
(2022)
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)
Review
Clinical Neurology
Surasak Wichaiyo, Warisara Parichatikanond, Wipharak Rattanavipanon
Summary: This review discusses the potential benefits of anti-GPVI antibody in the treatment of ischemic stroke based on preclinical and clinical studies. The findings suggest that anti-GPVI antibody may have a positive impact on reducing infarct volume and improving neurological function without increasing the risk of bleeding.
Article
Hematology
Masaaki Moroi, Isuru Induruwa, Richard W. Farndale, Stephanie M. Jung
Summary: The study found that dimeric GPVI acts as the receptor for fibrin, with different binding affinities to noncrosslinked and crosslinked fibrin clots. Its binding kinetics are similar to those obtained for binding to fibrinogen D-fragment and D-dimer, suggesting that the GPVI-binding site on fibrin(ogen) becomes exposed after fibrin formation or cleavage. Analysis of platelets bound to fibrin clots indicates that platelet GPVI binds to fibrin fibers comprising the clot.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Pharmacology & Pharmacy
Gi Suk Nam, Soyoung Kim, Yun-Suk Kwon, Min-Kyung Kim, Kyung-Soo Nam
Summary: MAP4K4 inhibitors reduce thrombus formation by regulating platelet activation, showing potential for the treatment of thrombosis.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Oliver Borst, Meinrad Gawaz
Summary: Subendothelial collagen exposed to platelets after rupture of atherosclerotic plaques is the main trigger of platelet activation and acute arterial thrombotic occlusion. Developing antiplatelet strategies that selectively inhibit atherothrombosis without interfering with bleeding control is an unmet clinical need. Platelet glycoprotein VI (GPVI) plays a crucial role in collagen-induced platelet activation and aggregation, making it a potential target for novel therapeutic strategies in thrombotic and inflammatory diseases.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Plant Sciences
Tae Woo Oh, Hyun Ju Do, Jae-Han Jeon, Kyungho Kim
Summary: The study demonstrated that quercitrin has inhibitory effects on platelet activity, can block thrombus formation, reduce infarct volume in stroke, and does not prolong bleeding time.
Article
Hematology
Albin Jeanne, Thomas Sarazin, Magalie Charle, Charlotte Kawecki, Alexandre Kauskot, Tobias Hedtke, Christian E. H. Schmelzer, Laurent Martiny, Pascal Maurice, Stephane Dedieu
Summary: The study shows that the TAX2 peptide can significantly reduce platelet aggregation and interaction with collagen, and delay arterial thrombus formation, representing a potential antithrombotic agent.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Eduardo Fuentes
Summary: Antiplatelet therapy aims to reduce the risk of thrombotic events by inhibiting platelet adhesion pathways mediated by GPVI. Blocking or antibody-mediated depletion of GPVI is a promising approach for the effective and safe prevention of thrombotic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Mei-Ling Wu, Xiao Zou, Xiao-Yu Chen, Kai-Ting Ma, Chu Chen, Neng-Wei Yu, Lu Yu, Jun-Rong Du
Summary: This study found that CD21 has a dose-dependent neuroprotective effect against thrombosis and brain damage caused by ischemic stroke in rats. It regulates the platelet-NET-thrombin axis, reduces NET formation, and inhibits inflammatory response by activating the AMPK pathway, thus protecting against ischemic brain injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Neurosciences
Michael Bieber, Michael K. Schuhmann, Alexander M. Kollikowski, David Stegner, Bernhard Nieswandt, Mirko Pham, Guido Stoll
Summary: Research has shown that blocking the activatory platelet receptor can delay the progression of neocortical infarction in acute ischemic stroke caused by large vessel occlusion, as well as mitigate the local vascular recruitment of neutrophils and T-cells. This experimental data supports ongoing clinical trials of blocking platelet GPVI in acute ischemic stroke.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Pharmacology & Pharmacy
Belay Tesfamariam, Steven C. Wood
Summary: Activated platelets protect circulating tumor cells from shear stress and promote their evasion from immune surveillance. They release transforming growth factor-81 (TGF-81) into the tumor microenvironment, inducing phenotypic changes that facilitate tumor cell dissemination and metastasis. Targeting the GPVI/FcR gamma-chain complex could potentially disrupt the platelet-tumor cell interaction without interfering with hemostasis.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Cell Biology
Xianghui Zhou, Xin Zhou, Ruirui Zhu, Zhangyin Ming, Zhipeng Cheng, Yu Hu
Summary: Our study found that oleic acid can inhibit platelet activation and reduce thrombogenesis by inhibiting the phosphorylation of multiple signaling molecules, providing new insights into the research and development of antiplatelet drugs.
CELL COMMUNICATION AND SIGNALING
(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
Cell Biology
Hari Hara Sudhan Lakshmanan, Alexander R. Melrose, Anna-Liisa Sepp, Annachiara Mitrugno, Anh T. P. Ngo, Ayesha Khader, Rachel Thompson, Daniel Sallee, Jiaqing Pang, Pierre H. Mangin, Martine Jandrot-Perrus, Joseph E. Aslan, Owen J. T. McCarty
Summary: In this study, it was demonstrated that recombinant human nidogen-1 supports platelet adhesion and activates platelets in a kinase-dependent manner downstream. Platelet adhesion to nidogen-1 was found to activate the IKK complex, while pharmacological inhibition of IKK blocked platelet spreading on nidogen. Overall, these results suggest that nidogen may play a redundant role in hemostasis by activating platelets downstream of GPVI.
Article
Food Science & Technology
Sabrina Karim-Silva, Alessandra Becker-Finco, Isabella Gizzi Jiacomini, Fanny Boursin, Arnaud Leroy, Magali Noiray, Juliana de Moura, Nicolas Aubrey, Philippe Billiald, Larissa M. Alvarenga
Article
Hematology
Muhammad Usman Ahmed, Valeria Kaneva, Stephane Loyau, Dmitry Nechipurenko, Nicolas Receveur, Marion Le Bris, Emily Janus-Bell, Melusine Didelot, Antoine Rauch, Sophie Susen, Nabil Chakfe, Francois Lanza, Elizabeth E. Gardiner, Robert K. Andrews, Mikhail Panteleev, Christian Gachet, Martine Jandrot-Perrus, Pierre H. Mangin
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2020)
Article
Pharmacology & Pharmacy
Lionel Renaud, Kristell Lebozec, Christine Voors-Pette, Peter Dogterom, Philippe Billiald, Martine Jandrot Perrus, Yannick Pletan, Matthias Machacek
JOURNAL OF CLINICAL PHARMACOLOGY
(2020)
Article
Cell Biology
Stephane Loyau Inserm, Dorothee Faille, Philippe Gautier, Paquita Nurden, Martine Jandrot-Perrus, Nadine Ajzenberg
Summary: Acquired deficiencies in platelet glycoprotein VI are rare and usually associated with immune thrombocytopenia. This case report describes a male patient with an immune GPVI deficiency linked to a mutation in the alpha-actinin gene, who was successfully treated with dual antiplatelet therapy without any bleeding complications.
Article
Hematology
Joachim C. Mertens, William Boisseau, Dorien Leenaerts, Lucas Di Meglio, Stephane Loyau, Anne-Marie Lambeir, Celina Ducroux, Martine Jandrot-Perrus, Jean-Baptiste Michel, Mikael Mazighi, Dirk Hendriks, Jean-Philippe Desilles
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2020)
Article
Hematology
Gina Perrella, Jingnan Huang, Isabella Provenzale, Frauke Swieringa, Floor C. J. Heubel-Moenen, Richard W. Farndale, Mark Roest, Paola E. J. van der Meijden, Mark Thomas, Robert A. S. Ariens, Martine Jandrot-Perrus, Steve P. Watson, Johan W. M. Heemskerk
Summary: The study revealed that fibrin fibers play a consolidating role in microthrombus formation through nonredundant signaling of platelet glycoprotein VI and integrin alpha IIb beta 3 via Syk and low-level Ca2+ rises, even in the absence of thrombin, leading to minimal thrombin generation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Letter
Hematology
Soumaya Jadoui, Ophelie Le Chapelain, Veronique Ollivier, Ali Mostefa-Kara, Lucas Di Meglio, Sebastien Dupont, Angele Gros, Mialitiana Solo Nomenjanahary, Jean-Philippe Desilles, Mikael Mazighi, Bernhard Nieswandt, Stephane Loyau, Martine Jandrot-Perrus, Pierre H. Mangin, Benoit Ho-Tin-Noe
Article
Cell Biology
Francois Delvoye, Stephane Loyau, Julien Labreuche, Guillaume Taylor, Benjamin Maier, Michel Piotin, Raphael Blanc, Simon Escalard, Lucas Di Meglio, Malek Ben Maacha, Hocine Redjem, Stanislas Smajda, Gabriele Ciccio, Solene Hebert, Candice Sabben, Martine Jandrot-Perrus, Alain Maertens De Noordhout, Mikael Mazighi, Benoit Ho-Tin-Noe, Jean-Philippe Desilles
Summary: This study investigated the use of the glycoprotein IIb/IIIa antagonist abciximab in treating immediate reocclusion after mechanical thrombectomy for acute ischemic stroke. The results showed that abciximab treatment led to higher recanalization rates without increasing bleeding complications. In vitro experiments further demonstrated that abciximab effectively limits thrombus accretion by blocking platelet aggregation.
Editorial Material
Hematology
Alexandre Slater, Martine Jandrot-Perrus
Summary: The authors of this study report the structure of platelet glycoprotein VI complexed with collagen-related peptides and propose the structural basis of GPVI clustering on collagen fibers.
Article
Biochemistry & Molecular Biology
Isabella Gizzi Jiacomini, Martina Beltramino, Fanny Boursin, Joao Carlos Minozzo, Juliana Ferreira de Moura, Philippe Billiald, Larissa Magalhaes Alvarenga, Nicolas Aubrey
Summary: The use of monoclonal antibodies in therapy is expanding, with focus on safety, cost-effectiveness, and efficacy. Recombinant DNA technology is used for large-scale production, and strategies for humanization have been developed considering their heterologous origin and potential immunogenicity. This study introduced a mouse monoclonal antibody with binding and neutralizing abilities against spider venom toxins, and explored its humanization potential.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Ilaria De Simone, Constance C. F. M. J. Baaten, Martine Jandrot-Perrus, Jonathan M. Gibbins, Hugo ten Cate, Johan W. M. Heemskerk, Chris Jones, Paola E. J. van der Meijden
Summary: Platelet and coagulation activation are reciprocal processes, and factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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.
Letter
Hematology
Emily Janus-Bell, Muhammad Usman Ahmed, Nicolas Receveur, Clarisse Mouriaux, Bernhard Nieswandt, Elizabeth E. Gardiner, Christian Gachet, Martine Jandrot-Perrus, Pierre H. Mangin
THROMBOSIS AND HAEMOSTASIS
(2021)