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Platelets May 2022Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove... (Review)
Review
Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove successful in guiding treatment decisions for patients with cardiovascular disease, justifying further research into novel markers of platelet reactivity. Platelets contain a variety of microRNAs (miRNAs) and are a major contributor to the extracellular circulating miRNA pool. Levels of platelet-derived miRNAs in the circulation have been associated with different measures of platelet activation as well as antiplatelet therapy and have therefore been implied as potential new markers of platelet reactivity. In contrast to the assessment of platelet reactivity by current platelet function tests, miRNA measurements may enable assessment of platelet reactivity . It remains to be seen however, whether miRNAs may aid clinical diagnostics. Major limitations in the platelet miRNA research field remain the susceptibility to preanalytical variation, non-standardized sample preparation and data normalization that hampers inter-study comparisons. In this review, we provide an overview of the literature on circulating miRNAs as biomarkers of platelet activation, highlighting the underlying biology, the application in patients with cardiovascular disease and antiplatelet therapy and elaborating on technical limitations regarding their quantification in the circulation.
Topics: Biomarkers; Blood Platelets; Cardiovascular Diseases; Circulating MicroRNA; Humans; MicroRNAs; Platelet Activation; Platelet Aggregation Inhibitors
PubMed: 35264060
DOI: 10.1080/09537104.2022.2042236 -
Platelets 2020
Topics: Blood Platelets; Editorial Policies; Humans; Journal Impact Factor; Periodicals as Topic; Platelet Activation; Platelet Aggregation Inhibitors
PubMed: 31790625
DOI: 10.1080/09537104.2020.1694785 -
International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
Platelets Jun 2017Proteolytic shedding of the extracellular ectodomain of platelet receptors provides a key mechanism for irreversible loss of ligand-binding capacity, and for regulating... (Review)
Review
Proteolytic shedding of the extracellular ectodomain of platelet receptors provides a key mechanism for irreversible loss of ligand-binding capacity, and for regulating platelet function in health and disease. Platelets derived from megakaryocytes are small anucleate cells in peripheral blood, with the ability to rapidly adhere, become activated, and secrete an array of procoagulant and proinflammatory factors at sites of vascular injury or disease, and to form a platelet aggregate (thrombus) which is not only critical in normal hemostasis and wound healing, but in atherothrombotic diseases including myocardial infarction and ischemic stroke. Basic mechanisms of receptor shedding on platelets have important distinctions from how receptors on other cell types might be shed, in that shedding is rapidly initiated (within seconds to minutes) and occurs under altered shear conditions encountered in flowing blood or experimentally ex vivo. This review will consider the key components of platelet receptor shedding, that is, the receptor with relevant cleavage site, the (metallo)proteinase or sheddase and how its activity is regulated, and the range of known regulatory factors that control platelet receptor shedding including receptor-associated molecules such as calmodulin, factors controlling sheddase surface expression and activity, and other elements such as shear stress, plasma membrane properties, cellular activation status or age. Understanding these basic mechanisms of platelet receptor shedding is significant in terms of utilizing receptor surface expression or soluble proteolytic fragments as platelet-specific biomarkers and/or ultimately therapeutic targeting of these mechanisms to control platelet reactivity and function.
Topics: Blood Platelets; Humans; Platelet Activation; Platelet Adhesiveness
PubMed: 27778531
DOI: 10.1080/09537104.2016.1235690 -
Microbiology Spectrum Dec 2022Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate...
Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate platelets is believed to be an important virulence mechanism. While the interactions between bacteria and platelets have been described in detail for many Gram-positive pathogens, little research has been carried out with SBSEC in this respect. Twenty-six isolates of the four most common species and subspecies of SBSEC identified in bacteremia were collected, and interactions with platelets were investigated in platelet rich plasma (PRP) from three donors. Aggregation was studied using light-transmission aggregometry and platelet activation using flow cytometry detecting surface upregulation of CD62P. Platelets and serum were treated with different inhibitors to determine mechanisms involved in platelet aggregation and activation. Twenty-two of 26 isolates induced aggregation in at least one donor, and four isolates induced aggregation in all three donors. In PRP from donor 1, isolate SL1 induced a rapid aggregation with a median time of 70 s to reach 50% aggregation. Blockade of the platelet Fc-receptor or enzymatic cleavage of IgG abolished platelet activation and aggregation. The capacity for bacteria-induced platelet aggregation was also shown to be transferable between donors through serum. SBSEC mediates platelet aggregation in an IgG and IgG-Fc-receptor dependent manner. Bacterial activation of platelets through this pathway is common for many bacteria causing IE and could be a potential therapeutic target for the prevention and treatment of this infection. The capacity of bacteria to activate and aggregate platelets is believed to contribute to the pathogenesis of IE. The Streptococcus bovis/Streptococcus equinus complex (SBSEC) contains known IE-pathogens, but there is limited research on the different subspecies ability to interact with platelets and what signaling pathways are involved. This study reports that 22 of 26 tested isolates of different subspecies within SBSEC can induce aggregation, and that aggregation is host dependent. The Fc-IgG-receptor pathway was shown essential for platelet activation and aggregation. To the best of our knowledge, this is the first study that reports on platelet interactions of SBSEC-isolates other than Streptococcus gallolyticus subspecies as well as the first study to report of mechanisms of platelet interaction of SBSEC-isolates. It adds SBSEC to a group of bacteria that activate and aggregate platelets via the platelet Fc-receptor. This could be a potential therapeutic target for prevention of IE.
Topics: Streptococcus bovis; Platelet Activation; Platelet Aggregation; Blood Platelets; Immunoglobulin G
PubMed: 36374116
DOI: 10.1128/spectrum.01861-22 -
Seminars in Thrombosis and Hemostasis Jul 2024This article represents a republication of an article originally published in STH in 2005. This republication is to help celebrate 50 years of publishing for STH. The... (Review)
Review
This article represents a republication of an article originally published in STH in 2005. This republication is to help celebrate 50 years of publishing for STH. The original abstract follows.Platelets are specialized blood cells that play central roles in physiologic and pathologic processes of hemostasis, inflammation, tumor metastasis, wound healing, and host defense. Activation of platelets is crucial for platelet function that includes a complex interplay of adhesion and signaling molecules. This article gives an overview of the activation processes involved in primary and secondary hemostasis, for example, platelet adhesion, platelet secretion, platelet aggregation, microvesicle formation, and clot retraction/stabilization. In addition, activated platelets are predominantly involved in cross-talk to other blood and vascular cells. Stimulated "sticky" platelets enable recruitment of leukocytes at sites of vascular injury under high shear conditions. Platelet-derived microparticles as well as soluble adhesion molecules, sP-selectin and sCD40L, shed from the surface of activated platelets, are capable of activating, in turn, leukocytes and endothelial cells. This article focuses further on the new view of receptor-mediated thrombin generation of human platelets, necessary for the formation of a stable platelet-fibrin clot during secondary hemostasis. Finally, special emphasis is placed on important stimulatory and inhibitory signaling pathways that modulate platelet function.
Topics: Humans; Blood Platelets; Hemostasis; Platelet Activation; Platelet Adhesiveness; Signal Transduction; Platelet Aggregation
PubMed: 38086407
DOI: 10.1055/s-0043-1777305 -
Thrombosis Research Jun 2018Platelet activation plays an important role in the development of sepsis. During sepsis, platelet activation leads to endothelial cell injury and promotes neutrophil... (Review)
Review
Platelet activation plays an important role in the development of sepsis. During sepsis, platelet activation leads to endothelial cell injury and promotes neutrophil extracellular trap and microthrombus formation, exacerbating septic coagulation and inflammatory reactions. The resultant induction or aggravation of disseminated intravascular coagulation (DIC) leads to organ damage. Antiplatelet drugs can inhibit coagulation and inflammatory reactions in models of sepsis, reducing damage to organ function. Clinical studies suggest that aspirin may improve the prognosis of patients with sepsis. In conclusion, antiplatelet drugs are promising agents that can improve the prognosis of sepsis patients and are expected to become a new line of treatment. However, further clinical studies are required for validation.
Topics: Humans; Platelet Activation; Platelet Aggregation Inhibitors; Sepsis
PubMed: 29655000
DOI: 10.1016/j.thromres.2018.04.007 -
Blood Jul 2014The RNA code found within a platelet and alterations of that code continue to shed light onto the mechanistic underpinnings of platelet function and dysfunction. It is... (Review)
Review
The RNA code found within a platelet and alterations of that code continue to shed light onto the mechanistic underpinnings of platelet function and dysfunction. It is now known that features of messenger RNA (mRNA) in platelets mirror those of nucleated cells. This review serves as a tour guide for readers interested in developing a greater understanding of platelet mRNA. The tour provides an in-depth and interactive examination of platelet mRNA, especially in the context of next-generation RNA sequencing. At the end of the expedition, the reader will have a better grasp of the topography of platelet mRNA and how it impacts platelet function in health and disease.
Topics: Animals; Blood Platelets; Humans; Platelet Activation; RNA, Messenger; Transcription, Genetic
PubMed: 24904119
DOI: 10.1182/blood-2014-04-512756 -
Platelets Feb 2022Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In... (Review)
Review
Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In this review, we outline what is known about influenza interaction with human platelets, virion internalization, and viral RNA sensing, and the consequent impact on platelet function. We further discuss activation of platelets by IgG-influenza complexes and touch upon mechanisms of environmental platelet activation that relate to prothrombotic outcomes in patients during infection.
Topics: Blood Platelets; Humans; Influenza, Human; Platelet Activation
PubMed: 34369285
DOI: 10.1080/09537104.2021.1961710 -
Dermatology (Basel, Switzerland) 2021Psoriasis is an immune-mediated inflammatory skin disease in conjunction with the systemic inflammatory process. It appears to be related to increased risks of... (Review)
Review
BACKGROUND
Psoriasis is an immune-mediated inflammatory skin disease in conjunction with the systemic inflammatory process. It appears to be related to increased risks of cardiovascular disease events, especially in severe cases. The hemostatic balance is disrupted due to the prothrombotic bias in psoriasis, which might be mainly preserved by platelet hyperactivity. Platelets are also immune cells that initiate and regulate immune and inflammatory processes, except as the principal mediator of hemostasis and thrombosis, and platelet dysfunction is deeply involved in the pathogenesis of psoriasis.
SUMMARY
The aim of this study is to perform a review that expounds abnormal platelet function in psoriasis and explains the important role of platelets in the pathogenic mechanism of psoriasis in order to provide new targets for comprehensive medical treatment.
Topics: Blood Platelets; Humans; Platelet Activation; Psoriasis
PubMed: 32349003
DOI: 10.1159/000505536