Article
Multidisciplinary Sciences
Rouven Schulz, Medina Korkut-Demirbas, Gloria Colombo, Sandra Siegert
Summary: This study introduces a chemogenetic approach to study G protein-coupled receptors (GPCRs) by designing GPCR chimeras that can mimic the functions of the target receptors without knowing their immediate ligands. The researchers demonstrate the successful use of this approach in studying the beta 2-adrenergic receptor in microglia and its role in inflammation. The results show that the chimeric receptors exhibit similar responses to the endogenous receptors in terms of signaling pathways and cellular processes. This new approach allows for the investigation of cell type-specific pathways without the need for known ligands.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Diego Mezzano, Paul Harrison, Andrew L. Frelinger, Andrew D. Mumford, Patrizia Noris, Marie Lordkipanidze, Paolo Gresele
Summary: This study aimed to provide expert consensus guidance on the use of platelet secretion assays (PSAs) for diagnosing inherited platelet function disorders (IPFD). Through a survey and evaluation of 26 experts from 10 different countries, the study identified some general agreements and specific assays that are appropriate for measuring platelet secretion. However, there is a lack of consensus on many other PSAs, indicating the need for further standardization and validation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Neurosciences
Paula Ferrer-Raventos, Katrin Beyer
Summary: Platelets play a significant role in neurodegenerative diseases, especially in Alzheimer's disease, through different activation pathways. Besides modulating immune response, platelets also participate in synaptic plasticity and neuronal differentiation.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Pediatrics
Andrei K. Garzon Dasgupta, Alexey A. Martyanov, Anastasia A. Ignatova, Victor G. Zgoda, Galina A. Novichkova, Mikhail A. Panteleev, Anastasia N. Sveshnikova
Summary: This study showed that pediatric platelets have higher levels of proteins related to mitochondrial activity, proteasome activity, and vesicle transport. Additionally, pediatric platelets exhibited increased cytosolic calcium levels at rest, decreased calcium mobilization in response to ADP, and reduced granule release. These differences in protein composition and functional responses suggest that platelet behavior is age-dependent.
PEDIATRIC RESEARCH
(2023)
Article
Nanoscience & Nanotechnology
Gurunath Apte, Michael Hirtz, Thi-Huong Nguyen
Summary: This study examines the effect of various nanotopographical surfaces printed using fluidic force microscopy on platelets. The results show that both the hemispherical array and hexagonal tile structures can reduce surface stiffness and inhibit platelet adhesion. This suggests that nanopatterns can inhibit platelet activation on surfaces.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Review
Surgery
Arun Subramanian, Siobhan Delaney, Stephen J. X. Murphy, Deirdre R. Smith, Chika Offiah, Jean McMahon, Gert J. de Borst, A. Ross Naylor, George Hamilton, Justin A. Kinsella, Dominick J. H. McCabe
Summary: The objective of this study is to investigate the role of platelet biomarkers in the pathogenesis of vascular events and risk stratification in patients with asymptomatic or symptomatic atherosclerotic carotid stenosis. The study found that platelets are excessively activated in stenosis patients, especially in recently symptomatic patients. It was also observed that platelets may become more activated following carotid interventions. However, the current data do not support the use of platelet function/reactivity testing to guide antiplatelet therapy in clinical practice.
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
(2022)
Article
Plant Sciences
Yuejin Xue, Liyuan Zhang, Lusha Zhang, Wei Sun, Zhirui Fang, Yuze Leng, Mengyao Li, Xiuyun Ren, Rui Zhang, Yingxue Zhang, Lu Chen, Hong Wang
Summary: This study investigated the antithrombotic and antiplatelet mechanisms of Danshensu (DSS) using network pharmacology analysis and in vitro experiments. The results showed that DSS effectively inhibited platelet activation by reducing reactive oxygen species (ROS) burden and preventing the release of platelet mtDNA. Importantly, DSS did not increase bleeding risk, suggesting its potential as a promising candidate drug for thrombosis and cardiovascular disease therapeutics.
Article
Plant Sciences
Jiang Jiang, Dengping Liu, Yuanyuan Wang, Wei Li, Zhihui Hong, Jianzhong An, Shigang Qiao, Zhanli Xie
Summary: The research found that GLA can alleviate liver dysfunction in the mouse model of sepsis. GLA-treated mice displayed lower complement activation and liver dysfunction after E. coli infection. GLA inhibited platelet activation through the RIP1/RIP3/AKT pathway and downregulated C3aR expression on the platelets, thereby inhibiting liver injury and dysfunction due to excessive complement activation.
Review
Physiology
Erika Moreno, Diana Pacheco-Alvarez, Maria Chavez-Canales, Stephanie Elizalde, Karla Leyva-Rios, Gerardo Gamba
Summary: The thiazide sensitive Na+:Cl- cotransporter (NCC) is crucial for salt reabsorption and blood pressure regulation. It has been extensively studied, with its structure, function, and kinetics elucidated. Cryo-EM has provided high-resolution structures, confirming essential glycosylation sites and the inverted conformation of specific regions. This review provides an overview of the research on the structure-function relationship of NCC, from the early biochemical studies to the recent cryo-EM structures.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Hematology
Jacobina Kristiansen, Erik L. Grove, Oliver Buchhave Pedersen, Steen D. Kristensen, Anne-Mette Hvas
Summary: This study systematically summarized the effect of regular exercise training on platelet function in patients with cardiovascular disease (CVD) and healthy individuals. The results showed that regular exercise training does not have a clear impact on platelet function.
THROMBOSIS RESEARCH
(2023)
Review
Hematology
Oliver Buchhave Pedersen, Leonardo Pasalic, Peter H. Nissen, Erik Lerkevang Grove, Steen Dalby Kristensen, Anne-Mette Hvas
Summary: This study aimed to summarize the current literature on dynamic changes in platelet activity analyzed by flow cytometry in patients with acute coronary syndromes (ACS). The results showed that platelet activity was lower at follow-up than at baseline in ACS patients, indicating a potential decrease in the risk of recurrent cardiovascular events. However, some patients exhibited sustained high platelet activity from baseline to follow-up, suggesting a continued risk of recurrent cardiovascular events.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2022)
Review
Hematology
Jeppe Lundholm Stadarfeld Jensen, Claus Vinter Bodker Hviid, Christine Lodberg Hvas, Steffen Christensen, Anne-Mette Hvas, Julie Brogaard Larsen
Summary: Patients with acute kidney injury (AKI) have an increased risk of bleeding due to acquired platelet dysfunction. Platelet aggregation is reduced in AKI patients in non-ICU settings, but not in ICU settings except when renal replacement therapy is involved. Thrombocytopenia is frequent in AKI and is often predictive of mortality. However, platelet function is not different between AKI and non-AKI patients and is not associated with bleeding in AKI.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2023)
Article
Immunology
Emmanuel Boadi Amoafo, Philomena Entsie, Samara Albayati, Glenn P. Dorsam, Satya P. Kunapuli, Laurie E. Kilpatrick, Elisabetta Liverani
Summary: Sepsis, a serious infection-related clinical syndrome with high mortality, may exhibit sex-related differences in immune response. Purinergic signaling, a sex-specific regulatory mechanism in immune cell physiology, may play a role in sepsis. Blocking the ADP-receptor P2Y(12) was protective in male mice during sepsis, but not in female mice. There may be sex-related differences in modulating P2Y(12) or P2Y(1) signaling pathways during sepsis. Additionally, sex-dependent effects were observed in human T lymphocytes. Targeting purinergic signaling shows promise as a therapy for sepsis, but sex-specific drug targeting needs further investigation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Erika Moreno, Consuelo Plata, Norma Vazquez, Dulce Maria Oropeza-Viveros, Diana Pacheco-Alvarez, Lorena Rojas-Vega, Viridiana Olin-Sandoval, Gerardo Gamba
Summary: The thiazide-sensitive Na+-Cl- cotransporter (NCC) is a major pathway for salt reabsorption in the kidney, and its inhibition with thiazides is commonly used for treating arterial hypertension. The eel, however, has two genes encoding NCC, with eNCC alpha expressed in the kidney and eNCC beta in the rectum. The study found that the eNCC beta, unlike the European counterpart, is resistant to thiazides. Additionally, both eNCC beta and jNCC beta have high transport capacity and display electrogenic properties dependent on chloride ions.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Hematology
Daniel Bergemalm, Sofia Ramstrom, Caroline Kardeby, Kjell Hultenby, Anna Gothlin Eremo, Carina Sihlbom, Jorgen Bergstrom, Jan Palmblad, Maria Astrom
Summary: In X-linked thrombocytopenia with thalassemia, male hemizygous patients with the mutation p.R216Q in the GATA1 gene exhibit macrothrombocytopenia, bleeding tendency, and beta-thalassemia traits. Studies on Swedish XLTT families showed abnormal blood test results, altered protein levels in blood platelets, and functional deficiencies in platelet alpha- and dense granules. The findings suggest a potential link between these protein and functional alterations and the increased bleeding tendency observed in XLTT patients.
Article
Peripheral Vascular Disease
Maximilian Tscharre, Silvia Lee, Christoph W. Kopp, Simon Panzer, Thomas Gremmel
Summary: Structural aspects of red blood cells, specifically mean corpuscular volume (MCV), are linked to cardiovascular outcomes in patients with peripheral artery disease (PAD). Low MCV is associated with an increased risk of adverse events and correlates with platelet reactivity during dual antiplatelet therapy (DAPT). These findings suggest that MCV may serve as a potential marker for predicting adverse outcomes in patients with PAD undergoing infrainguinal stenting.
Article
Cardiac & Cardiovascular Systems
Silvia Lee, Patricia P. Wadowski, Timothy Hoberstorfer, Constantin Weikert, Joseph Pultar, Christoph W. Kopp, Simon Panzer, Thomas Gremmel
Summary: The study found that hyperuricemia is associated with increased residual platelet reactivity in patients treated with clopidogrel and prasugrel, but not in those treated with ticagrelor.
CARDIOVASCULAR DRUGS AND THERAPY
(2021)
Article
Biochemical Research Methods
Benjamin E. J. Spurgeon, Alan D. Michelson, Andrew L. Frelinger
Summary: Platelets play key roles in biological processes and can be heterogeneous, with distinct subsets performing specialized functions. The study highlights the importance of anticoagulant choice, antibody cocktail storage, sample density, and instrument setup for reproducibility in platelet subset analysis. Panel design, compensation, clustering, and dimension reduction techniques are crucial for mapping platelet heterogeneity across different samples.
Article
Hematology
Stacy E. Croteau, Andrew L. Frelinger, Anja J. Gerrits, Alan D. Michelson
Summary: Decreased platelet surface phosphatidylserine expression measured by annexin V binding predicts increased bleeding in severe FVIII deficient patients on prophylaxis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Multidisciplinary Sciences
Bogdan Neculaes, Andrew L. Frelinger, Anja J. Gerrits, Thomas Gremmel, Emma E. Forde, Steven Klopman, Sabrina L. Carmichael, Alan D. Michelson
Summary: PEF-activated PRP can be controlled and adjusted for the release of growth factors, serotonin and hemoglobin by adjusting voltage, pulse width and calcium concentration, potentially offering advantages for wound healing compared to standard bovine thrombin-activated PRP.
Article
Hematology
Andrew L. Frelinger, Jose Rivera, David E. Connor, Kathleen Freson, Andreas Greinacher, Paul Harrison, Shinji Kunishima, Marie Lordkipanidze, Alan D. Michelson, Sofia Ramstrom, Paolo Gresele
Summary: Flow cytometry is increasingly used in the study of platelet disorders, but there is wide variation in specific reagents, methods, and equipment used, making interpretation and comparison of results difficult. An expert consensus was obtained on instrument and reagent standardization, methods, reporting, and quality control, but uncertainty remains in pre-analytical variables and clinical utility. Lack of consensus on the acceptability of anticoagulants such as heparin for platelet tests indicates the need for further research.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Cardiac & Cardiovascular Systems
Thomas Gremmel, Alan D. Michelson, Patricia P. Wadowski, Joseph Pultar, Constantin Weikert, Maximilian Tscharre, Silvia Lee, Simon Panzer, Andrew L. Frelinger
Summary: The study found that in the absence of ACS, women had higher platelet activation in response to TRAP, while there was no significant difference between men and women in ACS patients. The occurrence of ischemic endpoints did not differ significantly between men and women in ACS patients.
Article
Biochemical Research Methods
Benjamin E. J. Spurgeon, Andrew L. Frelinger
Summary: Platelets are small anucleate blood cells that contribute to hemostasis, immunity, and inflammation. They can be partitioned into subsets with specialized functions and divergent abilities based on their repertoire of surface receptors.
Article
Chemistry, Medicinal
Maximilian Tscharre, Franziska Wittmann, Daniela Kitzmantl, Silvia Lee, Beate Eichelberger, Patricia P. Wadowski, Gunther Laufer, Dominik Wiedemann, Simon Panzer, Thomas Perkmann, Daniel Zimpfer, Thomas Gremmel
Summary: In LVAD patients receiving aspirin and phenprocoumon, GDF-15 is inversely correlated with residual platelet reactivity through PAR-1.
Article
Hematology
Diego Mezzano, Paul Harrison, Andrew L. Frelinger, Andrew D. Mumford, Patrizia Noris, Marie Lordkipanidze, Paolo Gresele
Summary: This study aimed to provide expert consensus guidance on the use of platelet secretion assays (PSAs) for diagnosing inherited platelet function disorders (IPFD). Through a survey and evaluation of 26 experts from 10 different countries, the study identified some general agreements and specific assays that are appropriate for measuring platelet secretion. However, there is a lack of consensus on many other PSAs, indicating the need for further standardization and validation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Patricia P. Wadowski, Benjamin Panzer, Alicja Jozkowicz, Christoph W. Kopp, Thomas Gremmel, Simon Panzer, Renate Koppensteiner
Summary: Platelet-endothelial interactions play a crucial role in microcirculatory function and tissue homeostasis. COVID-19 disrupts the delicate balance between platelets and the vessel wall, leading to endothelial damage, microthrombosis, and tissue ischemia. In this opinion paper, we discuss the pathological processes that contribute to endothelial activation and thrombus formation, which may drive the deterioration of severe COVID-19 cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Benjamin E. J. Spurgeon, Andrew L. Frelinger III
Summary: This study developed a 16-color panel for analyzing platelets in human whole blood using spectral flow cytometry. The panel includes clinical relevant markers and an optimized protocol for high-parameter phenotyping, allowing the analysis of platelet phenotype and function.
Review
Cell Biology
Benjamin Panzer, Christoph W. Kopp, Christoph Neumayer, Renate Koppensteiner, Alicja Jozkowicz, Michael Poledniczek, Thomas Gremmel, Bernd Jilma, Patricia P. Wadowski
Summary: Toll-like receptors (TLRs) play a critical role in viral infections by inducing pro-inflammatory responses and disrupting vascular homeostasis. The injury to the vessel wall leads to pro-thrombotic processes and eventually causes micro-vessel plugging and tissue necrosis. TLRs also directly contribute to virus sensing and platelet activation. Upregulation of von Willebrand factor release and extra-cellular trap formation by TLRs further enhance thrombotic processes during inflammation. This review focuses on TLR signaling pathways in humans, which provoke pro-thrombotic responses during viral infections, particularly in individuals with cardiovascular diseases.
Article
Cardiac & Cardiovascular Systems
Patricia P. Wadowski, Joseph Pultar, Constantin Weikert, Beate Eichelberger, Maximilian Tscharre, Renate Koppensteiner, Simon Panzer, Thomas Gremmel
Summary: High platelet-to-lymphocyte ratio is associated with increased on-treatment platelet reactivity in prasugrel-treated patients with acute coronary syndrome, but not in patients on ticagrelor.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
(2022)
Article
Cardiac & Cardiovascular Systems
Patricia P. Wadowski, Joseph Pultar, Constantin Weikert, Beate Eichelberger, Irene M. Lang, Renate Koppensteiner, Simon Panzer, Thomas Gremmel
Summary: The study found a significant correlation in on-treatment residual ADP-inducible platelet reactivity measured by LTA and MEA in patients treated with prasugrel, but a lower correlation in those receiving ticagrelor. However, both LTA and MEA showed heterogeneous results in the classification of patients as responders or non-responders to P2Y(12) inhibition in both groups of patients.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
(2021)
