Article
Multidisciplinary Sciences
Isuru Induruwa, Harriet McKinney, Carly Kempster, Patrick Thomas, Joana Batista, Jean-Daniel Malcor, Arkadiusz Bonna, Joanne McGee, Elaine Bumanlag-Amis, Karola Rehnstrom, Sophie Ashford, Kenji Soejima, Willem Ouwehand, Richard Farndale, Kate Downes, Elizabeth Warburton, Masaaki Moroi, Stephanie Jung
Summary: Patients with stroke express more GPVI-dimer on their platelet surface at presentation, lasting at least until day-90 post-stroke. This finding provides evidence for anti-thrombotic targeting of GPVI-dimer in ischemic stroke.
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
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)
Article
Pharmacology & Pharmacy
Philipp Klingler, Marius Niklaus, Juergen Koessler, Katja Weber, Angela Koessler, Markus Boeck, Anna Kobsar
Summary: In platelets incubated for 24 hours, bortezomib mediates a slight attenuation of inhibitory signaling, associated with facilitated platelet aggregation using threshold agonist concentrations and enhanced adhesion on agonist-coated surfaces.
VASCULAR PHARMACOLOGY
(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
Biotechnology & Applied Microbiology
Brian Schnoor, Anne-Laure Papa
Summary: Lyophilized platelets, as a potential hemostatic agent, have long-term ambient storage capabilities and high biocompatibility, which make them a promising platform for drug delivery. The interactions between lyophilized platelets and fresh platelets have paradoxical effects on platelet adhesion and aggregation, which could have an impact for clinical applications.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Shukun Sun, Bao Qiao, Yu Han, Bailu Wang, Shujian Wei, Yuguo Chen
Summary: Platelets play a crucial role in normal hemostasis, but pathological platelet adhesion can lead to cardiovascular events. Traditional antithrombotic drugs have limited effects on platelet adhesion receptors, while posttranslational modifications (PTMs) can increase the functional diversity of these receptors and affect platelet processes. Targeting PTMs of platelet adhesion receptors with antithrombotic drugs may offer a new therapeutic approach.
PHARMACOLOGICAL RESEARCH
(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)
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)
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
Biochemistry & Molecular Biology
Simla Olgac, Abdurrahman Olgac, Idil Yenicesu, Yesim Ozkan
Summary: Cardiovascular diseases are a leading cause of death globally, highlighting the need for safe and effective antithrombotic drugs. This study identified two promising compounds as potential antiplatelet agents, which could serve as starting points for the design of new, potent, and selective GPVI receptor antagonists.
BIOORGANIC CHEMISTRY
(2022)
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)
Article
Biochemistry & Molecular Biology
Isabella Provenzale, Ilaria De Simone, Jonathan M. Gibbins, Johan W. M. Heemskerk, Paola E. J. van der Meijden, Chris I. Jones
Summary: This study investigated the roles of different extracellular matrix proteoglycans in platelet responses and thrombus formation. It was found that one proteoglycan (perlecan) enhanced platelet activation and promoted thrombus formation, but also reduced platelet adhesion under flow. This suggests that proteoglycans play an important role in platelet activation and thrombus formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Yana Roka-Moiia, Samuel Miller-Gutierrez, Daniel E. Palomares, Joseph E. Italiano, Jawaad Sheriff, Danny Bluestein, Marvin J. Slepian
Summary: Our study shows that exposure of platelets to elevated shear stress leads to downregulation of GPIb and alpha(IIb)beta(3) receptors on platelets, while increasing the generation of platelet-derived microparticles expressing elevated levels of these receptors. This mechanism limits platelet activation and aggregatory response induced by physiological stimuli.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Anne H. Tavenier, Renicus S. Hermanides, Enrico Fabris, Dominick J. Angiolillo, Arnoud W. J. van't Hof
Summary: Various strategies have been proposed to bridge the gap in platelet inhibition in STEMI patients undergoing primary PCI, aiming to optimize clinical outcomes in the acute phase.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)