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Blood Mar 2017The role of platelet adhesion, activation, and aggregation in acute atherothrombotic events such as myocardial infarction and stroke is well established. There is... (Review)
Review
The role of platelet adhesion, activation, and aggregation in acute atherothrombotic events such as myocardial infarction and stroke is well established. There is increasing evidence that platelet-endothelial interactions also contribute to early atherosclerotic plaque initiation and growth. Through these interactions, platelet-derived factors can contribute to the proinflammatory and mitogenic status of resident mural cells. Among the many putative mechanisms for platelet-endothelial interactions, increased endothelial-associated von Willebrand factor, particularly in a multimerized form, which interacts with platelet glycoproteins and integrins, is a major factor and represents a therapeutic target in early atherogenesis.
Topics: Atherosclerosis; Blood Platelets; Endothelial Cells; Humans; Platelet Adhesiveness; Platelet Aggregation; von Willebrand Factor
PubMed: 28174163
DOI: 10.1182/blood-2016-07-692673 -
Journal of Investigative Medicine : the... Apr 2020Platelets, cell fragments traditionally thought of as important only for hemostasis, substantially and dynamically contribute to the immune system's response to... (Review)
Review
Platelets, cell fragments traditionally thought of as important only for hemostasis, substantially and dynamically contribute to the immune system's response to infection. In addition, there is increasing evidence that externally active platelet entities, including platelet granules and platelet extracellular vesicles (PEVs), play a role not only in hemostasis, but also in inflammatory actions previously ascribed to platelets themselves. Given the functions of platelets and PEVs during inflammation and infection, their role in sepsis is being investigated. Sepsis is a condition marked by the dysregulation of the body's normal activation of the immune system in response to a pathogen. The mechanisms for controlling infection locally become detrimental to the host if they are applied systemically. Similar to cells traditionally ascribed to the immune system, including neutrophils, lymphocytes, and macrophages, platelets are instrumental in helping a host clear an infection, but are also implicated in the uncontrolled amplification of the immune response that leads to sepsis. Clearly, the function of platelets is more complicated than its simple structure and primary role in hemostasis initially suggest. This review provides an overview of platelet and platelet extracellular vesicle structure and function, highlighting the complex role platelets and PEVs play in the body in the context of infection and sepsis.
Topics: Animals; Blood Platelets; Extracellular Vesicles; Hemostasis; Humans; Immunity, Innate; Sepsis; Signal Transduction
PubMed: 31843956
DOI: 10.1136/jim-2019-001195 -
The American Journal of Cardiology Apr 2021Aspirin (ASA) has historically been one of the most important drugs in cardiology and has long been the cornerstone of antiplatelet therapy. Although its role in acute... (Review)
Review
Aspirin (ASA) has historically been one of the most important drugs in cardiology and has long been the cornerstone of antiplatelet therapy. Although its role in acute coronary syndrome remains undisputed, emerging data suggest that reappraisal of the efficacy of long-term ASA in some primary and secondary prevention may be warranted. The aim of this review is to place these new results in the context of previous evidence on aspirin by appraising the current body of evidence on its use of for cardiovascular diseases. This overview first summarizes the history of the discovery of aspirin, as well as its pharmacology and the concept of ASA resistance. We subsequently recapitulate the evidence of ASA on primary prevention and secondary prevention starting from the classical studies in order to serve as an introductory background to the examination of the most recent clinical trials that will be performed in the rest of the articles of this Supplement. Although the benefit of ASA in acute coronary syndrome remains incontrovertible, emerging evidence challenge the universal need for primary prevention, or for lifelong treatment in secondary prevention or all adults with stable coronary disease who are at highest risk for ASA-induced bleeding. The role of aspirin is quickly changing in recent times and this review provides a review for the clinician about the current role of this drug in cardiovascular care.
Topics: Aspirin; Blood Platelets; Humans; Platelet Aggregation Inhibitors
PubMed: 33706986
DOI: 10.1016/j.amjcard.2020.12.018 -
Clinical Science (London, England :... Nov 2020Platelets have a predominant role in haemostasis, the maintenance of blood volume and emerging roles as innate immune cells, in wound healing and in inflammatory... (Review)
Review
Platelets have a predominant role in haemostasis, the maintenance of blood volume and emerging roles as innate immune cells, in wound healing and in inflammatory responses. Platelets express receptors that are important for platelet adhesion, aggregation, participation in inflammatory responses, and for triggering degranulation and enhancing thrombin generation. They carry a cargo of granules bearing enzymes, adhesion molecules, growth factors and cytokines, and have the ability to generate reactive oxygen species. The platelet is at the frontline of a host of cellular responses to invading pathogens, injury, and infection. Perhaps because of this intrinsic responsibility of a platelet to rapidly respond to thrombotic, pathological and immunological factors as part of their infantry role; platelets are susceptible to targeted attack by the adaptive immune system. Such attacks are often transitory but result in aberrant platelet activation as well as significant loss of platelet numbers and platelet function, paradoxically leading to elevated risks of both thrombosis and bleeding. Here, we discuss the main molecular events underlying immune-based platelet disorders with specific focus on events occurring at the platelet surface leading to activation and clearance.
Topics: Animals; Blood Platelet Disorders; Blood Platelets; Endothelial Cells; Hemostasis; Humans; Models, Biological
PubMed: 33140828
DOI: 10.1042/CS20191101 -
Arteriosclerosis, Thrombosis, and... Apr 2018
Review
Topics: Animals; Blood Platelets; Cardiovascular Diseases; Drug Design; Humans; Molecular Targeted Therapy; Platelet Activation; Platelet Aggregation Inhibitors; Signal Transduction
PubMed: 29563117
DOI: 10.1161/ATVBAHA.118.310224 -
BioMed Research International 2016Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, mediating inflammatory... (Review)
Review
Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, mediating inflammatory and immunomodulatory activities. Our knowledge about how platelets modulate inflammatory and immunity has greatly improved in recent years. In this review, we discuss recent advances in the pathways of platelet activation and potential application of platelet activation biomarkers to diagnosis and prediction of disease states.
Topics: Animals; Biomarkers; Blood Platelets; Humans; Immunomodulation; Inflammation; Platelet Activation
PubMed: 27403440
DOI: 10.1155/2016/9060143 -
Platelets Mar 2018The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical... (Review)
Review
The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical capacities has enabled the genetic investigation of human traits and disease in thousands to now millions of participants. Investigators have taken advantage of these advancements to gain insight into platelet biology and the platelet's role in human disease. To do so, large human genetics studies have examined the association of genetic variation with two quantitative traits measured in many population and patient based cohorts: platelet count (PLT) and mean platelet volume (MPV). This article will review the many human genetic strategies-ranging from genome-wide association study (GWAS), Exomechip, whole exome sequencing (WES), to whole genome sequencing (WGS)-employed to identify genes and variants that contribute to platelet traits. Additionally, we will discuss how these investigations have examined and interpreted the functional implications of these newly identified genetic factors and whether they also impart risk to human disease. The depth and size of genetic, phenotypic, and other -omic data are primed to continue their growth in the coming years and provide unprecedented opportunities to gain critical insights into platelet biology and how platelets contribute to disease.
Topics: Blood Platelets; Female; Humans; Male; Mean Platelet Volume; Platelet Count
PubMed: 28649937
DOI: 10.1080/09537104.2017.1317732 -
Frontiers in Immunology 2020Platelets are small anucleate cells that are essential for many biological processes including hemostasis, thrombosis, inflammation, innate immunity, tumor metastasis,... (Review)
Review
Platelets are small anucleate cells that are essential for many biological processes including hemostasis, thrombosis, inflammation, innate immunity, tumor metastasis, and wound healing. Platelets circulate in the blood and in order to perform all of their biological roles, platelets must be able to arrest their movement at an appropriate site and time. Our knowledge of how platelets achieve this has expanded as our ability to visualize and quantify discreet platelet events has improved. Platelets are exquisitely sensitive to changes in blood flow parameters and so the visualization of rapid intricate platelet processes under conditions found in flowing blood provides a substantial challenge to the platelet imaging field. The platelet's size (~2 μm), rapid activation (milliseconds), and unsuitability for genetic manipulation, means that appropriate imaging tools are limited. However, with the application of modern imaging systems to study platelet function, our understanding of molecular events mediating platelet adhesion from a single-cell perspective, to platelet recruitment and activation, leading to thrombus (clot) formation has expanded dramatically. This review will discuss current platelet imaging techniques and , describing how the advancements in imaging have helped answer/expand on platelet biology with a particular focus on hemostasis. We will focus on platelet aggregation and thrombus formation, and how platelet imaging has enhanced our understanding of key events, highlighting the knowledge gained through the application of imaging modalities to experimental models and . Furthermore, we will review the limitations of current imaging techniques, and questions in thrombosis research that remain to be addressed. Finally, we will speculate how the same imaging advancements might be applied to the imaging of other vascular cell biological functions and visualization of dynamic cell-cell interactions.
Topics: Animals; Blood Platelets; Humans; Imaging, Three-Dimensional; Microscopy, Electron, Scanning; Optical Imaging
PubMed: 32082328
DOI: 10.3389/fimmu.2020.00078 -
Current Opinion in Hematology Sep 2017Although platelet endocytosis has been recognized in granule cargo loading and the trafficking of several platelet surface receptors, its acute physiological relevance... (Review)
Review
PURPOSE OF REVIEW
Although platelet endocytosis has been recognized in granule cargo loading and the trafficking of several platelet surface receptors, its acute physiological relevance is poorly understood as is its mechanism. The present review discusses the current understanding of platelet endocytosis and its implications for platelet function.
RECENT FINDINGS
Recent studies are beginning to identify and define the proteins that mediate platelet endocytosis. These studies have shown that platelets contain different endosomal compartments and may use multiple endocytic routes to take in circulating molecules and surface proteins. The studies have also shown that platelet endocytosis is involved in several aspects of platelet function such as signaling, spreading, and granule cargo loading.
SUMMARY
Mechanistic studies of platelet endocytosis have shown it to be not only involved in granule cargo loading but also in various other platelet functions important for hemostasis and beyond.
Topics: Animals; Biological Transport, Active; Blood Platelets; Endocytosis; Hemostasis; Humans; Signal Transduction
PubMed: 28650849
DOI: 10.1097/MOH.0000000000000366 -
Current Opinion in Hematology Sep 2014Stem cells are an important tool for the study of ex-vivo models of megakaryopoiesis and the production of functional platelets. In this manuscript, we review the... (Review)
Review
PURPOSE OF REVIEW
Stem cells are an important tool for the study of ex-vivo models of megakaryopoiesis and the production of functional platelets. In this manuscript, we review the optimization of megakaryocyte and platelet differentiation and discuss the mechanistic studies and disease models that have incorporated stem cell technologies.
RECENT FINDINGS
Mechanisms of cytoskeletal regulation and signal transduction have revealed insights into hierarchical dynamics of hematopoiesis, highlighting the close relationship between hematopoietic stem cells and cells of the megakaryocyte lineage. Platelet disorders have been successfully modeled and genetically corrected, and differentiation strategies have been optimized to the extent that utilizing stem cell-derived platelets for cellular therapy is feasible.
SUMMARY
Studies that utilize stem cells for the efficient derivation of megakaryocytes and platelets have played a role in uncovering novel molecular mechanisms of megakaryopoiesis, modeling and correcting relevant diseases, and differentiating platelets that are functional and scalable for translation into the clinic. Efforts to derive megakaryocytes and platelets from pluripotent stem cells foster the opportunity of a revolutionary cellular therapy for the treatment of multiple platelet-associated diseases.
Topics: Animals; Blood Platelets; Cell Differentiation; Cell Lineage; Humans; Megakaryocytes; Models, Biological; Stem Cells
PubMed: 25023469
DOI: 10.1097/MOH.0000000000000064