Molecular and Cellular Insights into Platelet Function

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Cardiovascular System".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 3161

Special Issue Editors


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Guest Editor
Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Grombühlstrasse 12, D-97080 Wuerzburg, Germany
Interests: cyclic nucleotides signaling; PKA; PKG; platelets
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Guest Editor
Department of Medical Physics, Physics Faculty, Lomonosov Moscow State University, 1 Leninskie Gory, 119991 Moscow, Russia
Interests: immune; platelet; thrombosis

Special Issue Information

Dear Colleagues,

Blood platelets are unique anuclear cells whose main function is to protect vascular integrity by forming hemostatic plugs, promoting blood coagulation, and regulating vessel wall status. They also moonlight as regulators of wound healing, fibrinolysis, regeneration and tissue remodeling, angiogenesis, lymphatic development, inflammation, and immunity. This multitude of functions, the high complexity of the inner structure, and an intricate signal transduction network make platelets a difficult and exciting object of research, while their involvement in vital physiological and pathological processes makes this research urgently important. Despite enormous progress in recent decades, platelets still hide numerous mysteries.

This Special Issue of Cells will highlight recent progress and discuss major obstacles in the platelet field through a collection of original research articles, reviews, and communications. We welcome all types of studies (including basic, methodological, technological, and computational ones) related to this topic to be submitted to this Special Issue.

Prof. Dr. Stepan Gambaryan
Dr. Mikhail A. Panteleev
Guest Editors

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Keywords

  • platelet
  • wound healing
  • fibrinolysis
  • regeneration and tissue remodeling
  • angiogenesis
  • lymphatic development
  • inflammation and immunity

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Published Papers (4 papers)

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Research

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17 pages, 2551 KiB  
Article
Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
by Carlos Zamora, Cesar Diaz-Torne, Maria Angels Ortiz, Patricia Moya, Hye Sang Park, Concepció Pitarch, Elisabet Cantó, Ruben Osuna-Gomez, Maria Mulet, Maisa Garcia-Arguinzonis, Diego Collado, Hector Corominas and Silvia Vidal
Cells 2025, 14(9), 625; https://doi.org/10.3390/cells14090625 - 22 Apr 2025
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Abstract
Background: Platelets (PLTs) from healthy donors (HD) modulate T lymphocyte responses but PLTs from rheumatoid arthritis (RA) patients contribute to persistent systemic inflammation. This suggests that PLTs from RA patients and HD have different immunomodulatory effects. Methods: Using cell culture, flow cytometry, proteomics, [...] Read more.
Background: Platelets (PLTs) from healthy donors (HD) modulate T lymphocyte responses but PLTs from rheumatoid arthritis (RA) patients contribute to persistent systemic inflammation. This suggests that PLTs from RA patients and HD have different immunomodulatory effects. Methods: Using cell culture, flow cytometry, proteomics, and ELISA, we compared PLTs from HD and RA patients and their effects on T lymphocyte activation and cytokine production. Results: HD PLTs suppressed T lymphocyte proliferation and IFNγ and TNF production, while RA PLTs exhibited reduced suppressive capacity. In the presence of RA PLTs, IFNγ levels correlated with T lymphocyte proliferation, greater disease activity, and anti-citrullinated protein antibodies (ACPA). Proteomic analysis revealed that RA PLTs show upregulation of proteins linked to acute-phase response and complement activation. RA PLTs secreted higher levels of soluble CD40L (sCD40L) and PDGF-BB that correlated with enhanced IFNγ production. Seropositive RA patients had higher levels of sCD40L, and these levels were predictive of disease remission in RA patients treated with anti-IL6R. sCD40L was found to enhance T lymphocyte activation and to contribute to increased pro-inflammatory cytokine production. Conclusions: This study highlights the diminished ability of RA PLTs to suppress T lymphocyte activation and that sCD40L can be a potential biomarker and therapeutic target in RA. Full article
(This article belongs to the Special Issue Molecular and Cellular Insights into Platelet Function)
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11 pages, 572 KiB  
Article
Platelet Function, Platelet Size and Content of Reticulated Platelets: Interactions in Patients Receiving Dual Antiplatelet Therapy
by Valeria V. Bodrova, Olga N. Shustova, Nina V. Golubeva, Amina K. Alieva, Vladislav V. Vlodzyanovsky, Dmitry V. Pevzner and Alexey V. Mazurov
Cells 2024, 13(20), 1712; https://doi.org/10.3390/cells13201712 - 16 Oct 2024
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Abstract
Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome [...] Read more.
Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy. Full article
(This article belongs to the Special Issue Molecular and Cellular Insights into Platelet Function)
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Review

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18 pages, 717 KiB  
Review
Platelet Reactive Oxygen Species, Oxidised Lipid Stress, Current Perspectives, and an Update on Future Directions
by Lih T. Cheah, Matthew S. Hindle, Jawad S. Khalil, Cedric Duval, Amanda J. Unsworth and Khalid M. Naseem
Cells 2025, 14(7), 500; https://doi.org/10.3390/cells14070500 - 27 Mar 2025
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Abstract
Blood platelets are anucleate cells that play a vital role in haemostasis, innate immunity, angiogenesis, and wound healing. However, the inappropriate activation of platelets also contributes to vascular inflammation, atherogenesis, and thrombosis. Platelet activation is a highly complex receptor-mediated process that involves a [...] Read more.
Blood platelets are anucleate cells that play a vital role in haemostasis, innate immunity, angiogenesis, and wound healing. However, the inappropriate activation of platelets also contributes to vascular inflammation, atherogenesis, and thrombosis. Platelet activation is a highly complex receptor-mediated process that involves a multitude of signalling intermediates in which Reactive Oxygen Species (ROS) are proposed to play an important role. However, like for many cells, changes in the balance of ROS generation and/or scavenging in disease states may lead to the adoption of maladaptive platelet phenotypes. Here, we review the diverse roles of ROS in platelet function and how ROS are linked to specific platelet activation pathways. We also examine how changes in disease, particularly the plasma oxidised low-density lipoprotein (oxLDL), affect platelet ROS generation and platelet function. Full article
(This article belongs to the Special Issue Molecular and Cellular Insights into Platelet Function)
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19 pages, 1181 KiB  
Review
Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps
by Christopher Sennett and Giordano Pula
Cells 2025, 14(5), 335; https://doi.org/10.3390/cells14050335 - 25 Feb 2025
Viewed by 707
Abstract
Neutrophil extracellular traps (NETs) have received significant attention in recent years for their role in both the immune response and the vascular damage associated with inflammation. Platelets have been described as critical components of NETs since the initial description of this physio-pathological response [...] Read more.
Neutrophil extracellular traps (NETs) have received significant attention in recent years for their role in both the immune response and the vascular damage associated with inflammation. Platelets have been described as critical components of NETs since the initial description of this physio-pathological response of neutrophils. Platelets have been shown to play a dual role as responders and also as stimulators of NETs. The direct interaction with DNA leads to the entrapment of platelets into NETs, a phenomenon that significantly contributes to the thrombotic complications of inflammation and neutrophil activation, while the direct and paracrine stimulation of neutrophils by platelets has been shown to initiate the process of NET formation. In this review, we provide a comprehensive description of our current understanding of the molecular mechanisms underlying the entrapping of platelets into NETs and, in parallel, the platelet-driven cellular responses promoting NET formation. We then illustrate established examples of the contribution of NETs to vascular pathologies, describe the important questions that remain to be answered regarding the contribution of platelets to NET formation and NET-dependent cardiovascular complication, and highlight the fundamental steps taken towards the application of our understanding of platelets’ contribution to NETs for the development of novel cardiovascular therapies. Full article
(This article belongs to the Special Issue Molecular and Cellular Insights into Platelet Function)
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