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International Journal of Molecular... Sep 2021The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a... (Review)
Review
The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.
Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Antiparasitic Agents; Antiviral Agents; Blood Platelets; Humans; Ribonucleases
PubMed: 34638568
DOI: 10.3390/ijms221910230 -
International Journal of Molecular... Feb 2023Platelets, traditionally known for their roles in hemostasis and coagulation, are the most prevalent blood component after erythrocytes (150,000-400,000 platelets/μL in... (Review)
Review
Platelets, traditionally known for their roles in hemostasis and coagulation, are the most prevalent blood component after erythrocytes (150,000-400,000 platelets/μL in healthy humans). However, only 10,000 platelets/μL are needed for vessel wall repair and wound healing. Increased knowledge of the platelet's role in hemostasis has led to many advances in understanding that they are crucial mediators in many other physiological processes, such as innate and adaptive immunity. Due to their multiple functions, platelet dysfunction is involved not only in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism, but also in several other disorders, such as tumors, autoimmune diseases, and neurodegenerative diseases. On the other hand, thanks to their multiple functions, nowadays platelets are therapeutic targets in different pathologies, in addition to atherothrombotic diseases; they can be used as an innovative drug delivery system, and their derivatives, such as platelet lysates and platelet extracellular vesicles (pEVs), can be useful in regenerative medicine and many other fields. The protean role of platelets, from the name of Proteus, a Greek mythological divinity who could take on different shapes or aspects, is precisely the focus of this review.
Topics: Humans; Blood Platelets; Hemostasis; Thrombosis; Blood Coagulation; Adaptive Immunity
PubMed: 36901997
DOI: 10.3390/ijms24054565 -
Aging Nov 2018
Topics: Animals; Blood Platelets; Calcium; Calcium Signaling; Filamins; Gene Expression Regulation; Humans; Platelet Aggregation
PubMed: 30401791
DOI: 10.18632/aging.101635 -
Journal of Thrombosis and Haemostasis :... Jul 2009Agonist-induced elevation in cytosolic Ca2+ concentrations is essential for platelet activation in hemostasis and thrombosis. It occurs through Ca2+ release from... (Review)
Review
Agonist-induced elevation in cytosolic Ca2+ concentrations is essential for platelet activation in hemostasis and thrombosis. It occurs through Ca2+ release from intracellular stores and Ca2+ entry through the plasma membrane (PM). Ca2+ store release is a well-established process involving phospholipase (PL)C-mediated production of inositol-1,4,5-trisphosphate (IP3), which in turn releases Ca2+ from the intracellular stores through IP3 receptor channels. In contrast, the mechanisms controlling Ca2+ entry and the significance of this process for platelet activation have been elucidated only very recently. In platelets, as in other non-excitable cells, the major way of Ca2+ entry involves the agonist-induced release of cytosolic sequestered Ca2+ followed by Ca2+ influx through the PM, a process referred to as store-operated calcium entry (SOCE). It is now clear that stromal interaction molecule 1 (STIM1), a Ca2+ sensor molecule in intracellular stores, and the four transmembrane channel protein Orai1 are the key players in platelet SOCE. The other major Ca2+ entry mechanism is mediated by the direct receptor-operated calcium (ROC) channel, P2X1. Besides these, canonical transient receptor potential channel (TRPC) 6 mediates Ca2+ entry through the PM. This review summarizes the current knowledge of platelet Ca2+ homeostasis with a focus on the newly identified Ca2+ entry mechanisms.
Topics: Blood Platelets; Calcium; Calcium Signaling; Homeostasis; Humans
PubMed: 19422456
DOI: 10.1111/j.1538-7836.2009.03455.x -
Blood Feb 2012Although platelets are the smallest cells in the blood, they are implied in various processes ranging from immunology and oncology to thrombosis and hemostasis. Many... (Review)
Review
Although platelets are the smallest cells in the blood, they are implied in various processes ranging from immunology and oncology to thrombosis and hemostasis. Many large-scale screening programs, genome-wide association, and "omics" studies have generated lists of genes and loci that are probably involved in the formation or physiology of platelets under normal and pathologic conditions. This creates an increasing demand for new and improved model systems that allow functional assessment of the corresponding gene products in vivo. Such animal models not only render invaluable insight in the platelet biology, but in addition, provide improved test systems for the validation of newly developed anti-thrombotics. This review summarizes the most important models to generate transgenic platelets and to study their influence on platelet physiology in vivo. Here we focus on the zebrafish morpholino oligonucleotide technology, the (platelet-specific) knockout mouse, and the transplantation of genetically modified human or murine platelet progenitor cells in myelo-conditioned mice. The various strengths and pitfalls of these animal models are illustrated by recent examples from the platelet field. Finally, we highlight the latest developments in genetic engineering techniques and their possible application in platelet research.
Topics: Animals; Animals, Genetically Modified; Blood Platelets; Gene Transfer Techniques; Humans; Mice; Models, Animal; Models, Biological; Platelet Transfusion; Thrombopoiesis; Zebrafish
PubMed: 22180441
DOI: 10.1182/blood-2011-10-381715 -
Journal of the American College of... Mar 2012Women are underrepresented in cardiovascular studies, even as their preponderance in the aging population steadily increases. Although concerns have been raised about... (Review)
Review
Women are underrepresented in cardiovascular studies, even as their preponderance in the aging population steadily increases. Although concerns have been raised about the differential benefit of antiplatelet medications for women, the propensity for increased bleeding among women has also been recognized. A better understanding of the factors contributing to the observed sex-related differences in platelet biology is warranted. These factors include differences in the frequency and expression of genetic polymorphisms affecting platelet responsiveness to agonists (with and without antiplatelet therapies), which might be obtained through population-based studies and in large controlled clinical trials; inflammatory marker levels and their influence on atherothrombotic risk, and the role of specific hormones in mediating platelet activation and function. Knowledge gained about these mechanistic factors might inform the development of sex-specific antithrombotic treatment regimens that confer optimized safety and efficacy.
Topics: Blood Platelets; Cardiovascular Diseases; Drugs, Investigational; Female; Humans; Platelet Aggregation Inhibitors
PubMed: 22381424
DOI: 10.1016/j.jacc.2011.09.075 -
Journal of Thrombosis and Haemostasis :... Jul 2011Common variant effects on human platelet function and response to anti-platelet treatment have traditionally been studied using candidate gene approaches involving a... (Review)
Review
Common variant effects on human platelet function and response to anti-platelet treatment have traditionally been studied using candidate gene approaches involving a limited number of variants and genes. These studies have often been undertaken in clinically defined cohorts. More recently, studies have applied genome-wide scans in larger population samples than prior candidate studies, in some cases scanning relatively healthy individuals. These studies demonstrate synergy with some prior candidate gene findings (e.g., GP6, ADRA2A) but also uncover novel loci involved in platelet function. Here, I summarise findings on common genetic variation influencing platelet development, function and therapeutics. Taken together, candidate gene and genome-wide studies begin to account for common variation in platelet function and provide information that may ultimately be useful in pharmacogenetic applications in the clinic. More than 50 loci have been identified with consistent associations with platelet phenotypes in ≥ 2 populations. Several variants are under further study in clinical trials relating to anti-platelet therapies. In order to have useful clinical applications, variants must have large effects on a modifiable outcome. Regardless of clinical applications, studies of common genetic influences, even of small effect, offer additional insights into platelet biology including the importance of intracellular signalling and novel receptors. Understanding of common platelet-related genetics remains behind parallel fields (e.g., lipids, blood pressure) due to challenges in phenotype ascertainment. Further work is necessary to discover and characterise loci for platelet function, and to assess whether these loci contribute to disease aetiologies or response to therapeutics.
Topics: Animals; Blood Platelets; Genetic Linkage; Genome-Wide Association Study; Humans; Platelet Aggregation Inhibitors; Polymorphism, Single Nucleotide; Quantitative Trait Loci
PubMed: 21781261
DOI: 10.1111/j.1538-7836.2011.04359.x -
Current Opinion in Hematology Sep 2012It is now well appreciated that megakaryocytes invest platelets with a diverse repertoire of messenger RNAs (mRNAs), which are competent for translation. Herein we... (Review)
Review
PURPOSE OF REVIEW
It is now well appreciated that megakaryocytes invest platelets with a diverse repertoire of messenger RNAs (mRNAs), which are competent for translation. Herein we describe what is currently known regarding the expression, function, and clinical significance of mRNAs in platelets.
RECENT FINDINGS
Although mRNA was detected in platelets nearly 30 years ago, we are only beginning to understand the roles of mRNA in platelet biology and human disease. Recent studies have shown that megakaryocytes specifically sort, rather than randomly transfer, mRNA to platelets during thrombopoiesis. As a result, platelets are released into the circulation with thousands of mRNAs. The emergence of next-generation RNA sequencing has demonstrated that platelet mRNAs possess classic structural features, which include untranslated regions and open reading frames. There is also growing evidence that platelet mRNA expression patterns are altered in human disease.
SUMMARY
Intense investigation of platelet mRNA has shed considerable light on predicted functions of platelets and identified previously unrecognized attributes of platelets. Lessons learned from platelet mRNA is presented in this review.
Topics: Blood Platelets; Humans; RNA, Messenger; Thrombopoiesis
PubMed: 22814651
DOI: 10.1097/MOH.0b013e328357010e -
Blood Mar 2016Platelets are anucleate cytoplasmic discs derived from megakaryocytes that circulate in the blood and have major roles in hemostasis, thrombosis, inflammation, and... (Review)
Review
Platelets are anucleate cytoplasmic discs derived from megakaryocytes that circulate in the blood and have major roles in hemostasis, thrombosis, inflammation, and vascular biology. Platelet transfusions are required to prevent the potentially life-threatening complications of severe thrombocytopenia seen in a variety of medical settings including cancer therapy, trauma, and sepsis. Platelets used in the clinic are currently donor-derived which is associated with concerns over sufficient availability, quality, and complications due to immunologic and/or infectious issues. To overcome our dependence on donor-derived platelets for transfusion, efforts have been made to generate in vitro-based platelets. Work in this area has advanced our understanding of the complex processes that megakaryocytes must undergo to generate platelets both in vivo and in vitro. This knowledge has also defined the challenges that must be overcome to bring in vitro-based platelet manufacturing to a clinical reality. This review will focus on our understanding of committed megakaryocytes and platelet release in vivo and in vitro, and how this knowledge can guide the development of in vitro-derived platelets for clinical application.
Topics: Animals; Blood Donors; Blood Platelets; Cell Culture Techniques; Cell Differentiation; Humans; Megakaryocytes; Platelet Transfusion
PubMed: 26787738
DOI: 10.1182/blood-2015-08-607929 -
International Journal of Molecular... Aug 2020The increasing discoveries regarding the biology and functions of platelets in the last decade undoubtedly show that these cells are one of the most biotechnological... (Review)
Review
The increasing discoveries regarding the biology and functions of platelets in the last decade undoubtedly show that these cells are one of the most biotechnological human cells. This review summarizes new advances in platelet biology, functions, and new concepts of biotech-educated platelets that connect advanced biomimetic science to platelet-based additive manufacturing for tissue regeneration. As highly responsive and secretory cells, platelets could be explored to develop solutions that alter injured microenvironments through platelet-based synthetic biomaterials with instructive extracellular cues for morphogenesis in tissue engineering beyond tissue regeneration 2.0.
Topics: Animals; Biotechnology; Blood Platelets; Tissue Engineering; Wound Healing
PubMed: 32842455
DOI: 10.3390/ijms21176061