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JCI Insight Jul 2023Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Increased platelet counts and activation are observed during the course of KD, and...
Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Increased platelet counts and activation are observed during the course of KD, and elevated platelet counts are associated with higher risks of developing intravenous immunoglobulin resistance and coronary artery aneurysms. However, the role of platelets in KD pathogenesis remains unclear. Here, we analyzed transcriptomics data generated from the whole blood of patients with KD and discovered changes in the expression of platelet-related genes during acute KD. In the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, LCWE injection increased platelet counts and the formation of monocyte-platelet aggregates (MPAs), upregulated the concentration of soluble P-selectin, and increased circulating thrombopoietin and interleukin 6 (IL-6). Furthermore, platelet counts correlated with the severity of cardiovascular inflammation. Genetic depletion of platelets (Mpl-/- mice) or treatment with an anti-CD42b antibody significantly reduced LCWE-induced cardiovascular lesions. Furthermore, in the mouse model, platelets promoted vascular inflammation via the formation of MPAs, which likely amplified IL-1B production. Altogether, our results indicate that platelet activation exacerbates the development of cardiovascular lesions in a murine model of KD vasculitis. These findings enhance our understanding of KD vasculitis pathogenesis and highlight MPAs, which are known to enhance IL-1B production, as a potential therapeutic target for this disorder.
Topics: Animals; Mice; Mucocutaneous Lymph Node Syndrome; Blood Platelets; Disease Models, Animal; Vasculitis; Inflammation
PubMed: 37279077
DOI: 10.1172/jci.insight.169855 -
Seminars in Thrombosis and Hemostasis Jul 2024
Topics: Blood Platelets; Humans
PubMed: 38588703
DOI: 10.1055/s-0044-1785653 -
Journal of Thrombosis and Haemostasis :... Jul 2023Platelets play a central role in the arrest of bleeding. The ability of platelets to engage with extracellular matrix proteins of the subendothelium has long been... (Review)
Review
Platelets play a central role in the arrest of bleeding. The ability of platelets to engage with extracellular matrix proteins of the subendothelium has long been recognized as a pivotal platelet attribute, underpinning adequate hemostasis. The propensity of platelets to rapidly bind and functionally respond to collagen was one of the earliest documented events in platelet biology. The receptor primarily responsible for mediating platelet/collagen responses was identified as glycoprotein (GP) VI and successfully cloned in 1999. Since that time, this receptor has held the attention of many research groups, and through these efforts, we now have an excellent understanding of the roles of GPVI as a platelet- and megakaryocyte-specific adheso-signaling receptor in platelet biology. GPVI is considered a viable antithrombotic target, as data obtained from groups across the world is consistent with GPVI being less involved in physiological hemostatic processes but participating in arterial thrombosis. This review will highlight the key aspects of GPVI contributions to platelet biology and concentrate on the interaction with recently identified ligands, with a focus on fibrin and fibrinogen, discussing the role of these interactions in the growth and stability of thrombi. We will also discuss important therapeutic developments that target GPVI to modulate platelet function while minimizing bleeding outcomes.
Topics: Humans; Blood Platelets; Collagen; Fibrin; Hemorrhage; Platelet Activation; Platelet Membrane Glycoproteins; Thrombosis
PubMed: 36990158
DOI: 10.1016/j.jtha.2023.03.022 -
Thrombosis Research Nov 2023Autophagy, the continuous recycling of intracellular building blocks, molecules, and organelles is necessary to preserve cellular function and homeostasis. In this... (Review)
Review
Autophagy, the continuous recycling of intracellular building blocks, molecules, and organelles is necessary to preserve cellular function and homeostasis. In this context, it was demonstrated that autophagy plays an important role in megakaryopoiesis, the development and differentiation of hematopoietic progenitor cells into megakaryocytes. Furthermore, in recent years, autophagic proteins were detected in platelets, anucleate cells generated by megakaryocytes, responsible for hemostasis, thrombosis, and a key cell in inflammation and host immune responses. In the last decade studies have indicated the occurrence of autophagy in platelets. Moreover, autophagy in platelets was subsequently demonstrated to be involved in platelet aggregation, adhesion, and thrombus formation. Here, we review the current knowledge about autophagy in platelets, its function, and clinical implications. However, at the advent of platelet autophagy research, additional discoveries derived from evolving work will be required to precisely define the contributions of autophagy in platelets, and to expand the ever increasing physiologic and pathologic roles these remarkable and versatile blood cells play.
Topics: Humans; Blood Platelets; Megakaryocytes; Thrombopoiesis; Thrombosis; Autophagy; Biology
PubMed: 36058760
DOI: 10.1016/j.thromres.2022.08.019 -
International Journal of Molecular... Sep 2023Kidney disease is a major global health concern, affecting millions of people. Nephrologists have shown interest in platelets because of coagulation disorders caused by... (Review)
Review
Kidney disease is a major global health concern, affecting millions of people. Nephrologists have shown interest in platelets because of coagulation disorders caused by renal diseases. With a better understanding of platelets, it has been found that these anucleate and abundant blood cells not only play a role in hemostasis, but also have important functions in inflammation and immunity. Platelets are not only affected by kidney disease, but may also contribute to kidney disease progression by mediating inflammation and immune effects. This review summarizes the current evidence regarding platelet abnormalities in renal disease, and the multiple effects of platelets on kidney disease progression. The relationship between platelets and kidney disease is still being explored, and further research can provide mechanistic insights into the relationship between thrombosis, bleeding, and inflammation related to kidney disease, and elucidate targeted therapies for patients with kidney disease.
Topics: Humans; Immunity, Innate; Blood Platelets; Hemostasis; Inflammation; Kidney Diseases; Disease Progression
PubMed: 37834171
DOI: 10.3390/ijms241914724 -
Platelets Dec 2023The anucleate human platelets contain a broad pattern of mRNAs and other RNA transcripts. The high quantitative similarity of mRNAs in megakaryocytes and platelets from... (Review)
Review
The anucleate human platelets contain a broad pattern of mRNAs and other RNA transcripts. The high quantitative similarity of mRNAs in megakaryocytes and platelets from different sources points to a common origin, and suggests a random redistribution of mRNA species upon proplatelet formation. A comparison of the classified platelet transcriptome (17.6k transcripts) with the identified platelet proteome (5.2k proteins) indicates an under-representation of: nuclear but not of other organellar proteins; membrane receptors and channels with low transcript levels; transcription/translation proteins; and so far uncharacterized proteins. In this review, we discuss the technical, normalization and database-dependent possibilities and challenges to come to a complete, genome-wide platelet transcriptome and proteome. Such a reference transcriptome and proteome can serve to further elucidate intra-subject and inter-subject differences in platelets in health and disease. Applications may also lay in the aid of genetic diagnostics.
Topics: Humans; Proteome; Blood Platelets; Transcriptome; Megakaryocytes; Databases, Factual; RNA, Messenger
PubMed: 37313659
DOI: 10.1080/09537104.2023.2224454 -
International Journal of Molecular... May 2024Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low... (Review)
Review
Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing -associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.
Topics: Humans; Thrombocytopenia; Thrombosis; Blood Platelets; Platelet Count; Heparin; Thrombotic Microangiopathies
PubMed: 38732176
DOI: 10.3390/ijms25094956 -
Platelets Dec 2023Proteomics tools provide a powerful means to identify, detect, and quantify protein-related details in studies of platelet phenotype and function. Here, we consider how...
Proteomics tools provide a powerful means to identify, detect, and quantify protein-related details in studies of platelet phenotype and function. Here, we consider how historical and recent advances in proteomics approaches have informed our understanding of platelet biology, and, how proteomics tools can be used going forward to advance studies of platelets. It is now apparent that the platelet proteome is comprised of thousands of different proteins, where specific changes in platelet protein systems can accompany alterations in platelet function in health and disease. Going forward, many challenges remain in how to best carry out, validate and interpret platelet proteomics experiments. Future studies of platelet protein post-translational modifications such as glycosylation, or studies that take advantage of single cell proteomics and top-down proteomics methods all represent areas of interest to profiling and more richly understanding platelets in human wellness and disease.
Topics: Humans; Blood Platelets; Proteomics; Phenotype; Proteome
PubMed: 37246523
DOI: 10.1080/09537104.2023.2217932 -
European Journal of Medical Research Sep 2023Platelets play a crucial role in cancer blood metastasis. Various cancer-related factors such as Toll-like receptors (TLRs), adenosine diphosphate (ADP) or extracellular... (Review)
Review
Platelets play a crucial role in cancer blood metastasis. Various cancer-related factors such as Toll-like receptors (TLRs), adenosine diphosphate (ADP) or extracellular matrix (ECM) can activate these small particles that function in hemostasis and thrombosis. Moreover, platelets induce Epithelial Mesenchymal Transition (EMT) to promote cancer progression and invasiveness. The activated platelets protect circulating tumor cells from immune surveillance and anoikis. They also mediate tumor cell arrest, extravasation and angiogenesis in distant organs through direct or indirect modulation, creating a metastatic microenvironment. This review summarizes the recent advances and progress of mechanisms in platelet activation and its interaction with cancer cells in metastasis.
Topics: Humans; Neoplasms; Blood Platelets; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 37770941
DOI: 10.1186/s40001-023-01342-w -
Biomolecules Nov 2023Platelets are anucleate cytoplasmic cell fragments that circulate in the blood, where they are involved in regulating hemostasis. Beyond their normal physiologic role,... (Review)
Review
Platelets are anucleate cytoplasmic cell fragments that circulate in the blood, where they are involved in regulating hemostasis. Beyond their normal physiologic role, platelets have emerged as versatile effectors of immune response. During an infection, cell surface receptors enable platelets to recognize viruses, resulting in their activation. Activated platelets release biologically active molecules that further trigger host immune responses to protect the body against infection. Their impact on the immune response is also associated with the recruitment of circulating leukocytes to the site of infection. They can also aggregate with leukocytes, including lymphocytes, monocytes, and neutrophils, to immobilize pathogens and prevent viral dissemination. Despite their host protective role, platelets have also been shown to be associated with various pathophysiological processes. In this review, we will summarize platelet and HIV interactions during infection. We will also highlight and discuss platelet and platelet-derived mediators, how they interact with immune cells, and the multifaceted responsibilities of platelets in HIV infection. Furthermore, we will give an overview of non-AIDS comorbidities linked to platelet dysfunction and the impact of antiretroviral therapy on platelet function.
Topics: Humans; HIV Infections; Inflammation; Blood Platelets; Hemostasis; Leukocytes
PubMed: 38002289
DOI: 10.3390/biom13111608