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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 -
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 -
Clinical & Developmental Immunology Mar 2005Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular... (Review)
Review
Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP) IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg) aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.
Topics: Animals; Blood Platelets; Cacao; Flavonoids; Humans; Platelet Activation
PubMed: 15712593
DOI: 10.1080/10446670410001722140 -
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 -
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 -
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 -
Critical Reviews in Oncology/hematology Mar 2015Platelets, once considered mediators of hemostasis and thrombosis, are now known to be involved in wound healing, inflammation, cardiovascular diseases, diabetes,... (Review)
Review
Platelets, once considered mediators of hemostasis and thrombosis, are now known to be involved in wound healing, inflammation, cardiovascular diseases, diabetes, arthritis, and cancer. Recent reports attest that platelets possess the cellular machinery to undergo apoptosis and that platelet apoptosis can be triggered by myriad stimuli including chemical and physical agonists, and pathophysiological conditions. Augmented rate of platelet apoptosis leads to thrombocytopenia, bleeding disorders and microparticle generation. Despite knowing the significant role of platelets in health and disease, and that any alterations in platelet functions can wreak havoc to the health, the offshoot reactions of therapeutic drugs on platelets and the far-reaching consequences are often neglected. The present review focuses on the impact of platelet apoptosis and the role of platelet-derived microparticles on different pathophysiological conditions. It also touches upon the effects of biologicals on platelets, and discusses the need to overcome the adverse effects of pro-apoptotic drugs through auxiliary therapy.
Topics: Apoptosis; Blood Platelet Disorders; Blood Platelets; Cell-Derived Microparticles; Humans
PubMed: 25439323
DOI: 10.1016/j.critrevonc.2014.11.002 -
Journal of Thrombosis and Haemostasis :... Jun 2013Recent work by the Encyclopedia of DNA Elements project showed that non-protein-coding RNAs account for an unexpectedly large proportion of the human genome. Among these... (Review)
Review
Recent work by the Encyclopedia of DNA Elements project showed that non-protein-coding RNAs account for an unexpectedly large proportion of the human genome. Among these non-coding RNAs are microRNAs (miRNAs), which are small RNA molecules that modulate protein expression by degrading mRNA or repressing mRNA translation. MiRNAs have been shown to play important roles in hematopoiesis including embryonic stem cell differentiation, erythropoiesis, granulocytopoiesis/monocytopoiesis, lymphopoiesis, and megakaryocytopoiesis. Additionally, disordered miRNA biogenesis and quantitative or qualitative alterations in miRNAs and their targets are associated with hematological pathologies. Platelets contain machinery to process pre-miRNAs into mature miRNAs, and specific platelet miRNA levels have been found to correlate with platelet reactivity. This review summarizes the current state of knowledge of miRNAs in megakaryocytes and platelets, and the exciting possibilities for future megakaryocyte-platelet transcriptome research.
Topics: Blood Platelets; Humans; MicroRNAs; Platelet Activation
PubMed: 23809137
DOI: 10.1111/jth.12214 -
International Journal of Molecular... May 2021Hsia and collaborators [...].
Hsia and collaborators [...].
Topics: Animals; Biomedical Research; Blood Platelets; Disease; Health; Humans; Platelet Aggregation Inhibitors; Platelet Count; Regenerative Medicine
PubMed: 34067024
DOI: 10.3390/ijms22094968 -
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