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The Journal of Cell Biology Jun 2013Circulating blood platelets are specialized cells that prevent bleeding and minimize blood vessel injury. Large progenitor cells in the bone marrow called megakaryocytes... (Review)
Review
Circulating blood platelets are specialized cells that prevent bleeding and minimize blood vessel injury. Large progenitor cells in the bone marrow called megakaryocytes (MKs) are the source of platelets. MKs release platelets through a series of fascinating cell biological events. During maturation, they become polyploid and accumulate massive amounts of protein and membrane. Then, in a cytoskeletal-driven process, they extend long branching processes, designated proplatelets, into sinusoidal blood vessels where they undergo fission to release platelets. Given the need for platelets in many pathological situations, understanding how this process occurs is an active area of research with important clinical applications.
Topics: Animals; Blood Platelets; Cell Differentiation; Cytoskeleton; Humans; Megakaryocytes
PubMed: 23751492
DOI: 10.1083/jcb.201304054 -
Current Opinion in Chemical Biology Apr 2023Platelets are small anucleate cell fragments (2-4 μm in diameter) in the blood, which play an essential role in thrombosis and hemostasis. Genetic or acquired platelet... (Review)
Review
Platelets are small anucleate cell fragments (2-4 μm in diameter) in the blood, which play an essential role in thrombosis and hemostasis. Genetic or acquired platelet dysfunctions are linked to bleeding, increased risk of thromboembolic events and cardiovascular diseases. Advanced proteomic approaches may pave the way to a better understanding of the roles of platelets in hemostasis, and pathophysiological processes such as inflammation, metastatic spread and thrombosis. Further insights into the molecular biology of platelets are crucial to aid drug development and identify diagnostic markers of platelet activation. Platelet activation is known to be an extremely rapid process and involves multiple post-translational mechanisms at sub second time scale, including proteolysis and phosphorylation. Multi-omics technologies and biochemical approaches can be exploited to precisely probe and define these posttranslational pathways. Notably, the absence of a nucleus in platelets significantly reduces the number of present proteins, simplifying mass spectrometry-based proteomics and metabolomics approaches.
Topics: Humans; Blood Platelets; Proteomics; Multiomics; Platelet Activation; Thrombosis
PubMed: 36689818
DOI: 10.1016/j.cbpa.2022.102253 -
Free Radical Biology & Medicine 1997This article reviews our current understanding of the role of oxygen free radicals in platelet activation. Several studies have indicated that platelets, in analogy to... (Review)
Review
This article reviews our current understanding of the role of oxygen free radicals in platelet activation. Several studies have indicated that platelets, in analogy to other circulating blood cells, are able to produce oxygen free radicals, which are likely to play an important role in the mechanism of platelet activation and aggregation. Platelet activation has been obtained with very low, physiologically relevant concentrations of radicals generated chemically, by leukocytes, and by hemoglobin derived from membrane leakage of erythrocytes. Knowledge of the role of reactive species in platelet physiology is relevant because platelets are brought into close contact with other cells capable of producing free radicals, such as neutrophils, macrophages, and endothelial cells, during the formation of thrombus. The physiopatological importance of these findings is high because it is now emerging that free radicals may have a role in the mechanism of atherosclerosis and its thrombotic complications, where the causative role of platelets is well documented. This background suggests therapeutic interventions with antioxidants as antiplatelet agents to improve the pharmacological effect of classical antiplatelet drug such as aspirin.
Topics: Antioxidants; Blood Platelets; Free Radicals; Humans; Oxygen; Platelet Activation
PubMed: 9034239
DOI: 10.1016/s0891-5849(96)00488-1 -
Platelets May 2020Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known... (Review)
Review
Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.
Topics: Aged; Aging; Animals; Blood Platelet Disorders; Blood Platelets; Comorbidity; Humans; Inflammation; Oxidative Stress; Platelet Activation; Risk Factors; Signal Transduction; Thrombosis
PubMed: 31524038
DOI: 10.1080/09537104.2019.1665641 -
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 -
International Journal of Molecular... Feb 2020Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may... (Review)
Review
Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.
Topics: Animals; Blood Platelets; Blood Specimen Collection; Humans; Musculoskeletal Diseases; Platelet-Rich Plasma
PubMed: 32079117
DOI: 10.3390/ijms21041328 -
Blood Dec 2018The ability to upregulate and downregulate surface-exposed proteins and receptors is a powerful process that allows a cell to instantly respond to its microenvironment.... (Review)
Review
The ability to upregulate and downregulate surface-exposed proteins and receptors is a powerful process that allows a cell to instantly respond to its microenvironment. In particular, mobile cells in the bloodstream must rapidly react to conditions where infection or inflammation are detected, and become proadhesive, phagocytic, and/or procoagulant. Platelets are one such blood cell that must rapidly acquire and manage proadhesive and procoagulant properties in order to execute their primary function in hemostasis. The regulation of platelet membrane properties is achieved via several mechanisms, one of which involves the controlled metalloproteolytic release of adhesion receptors and other proteins from the platelet surface. Proteolysis effectively lowers receptor density and reduces the reactivity of platelets, and is a mechanism to control robust platelet activation. Recent research has also established clear links between levels of platelet receptors and platelet lifespan. In this review, we will discuss the current knowledge of metalloproteolytic receptor regulation in the vasculature with emphasis on the platelet receptor system to highlight how receptor density can influence both platelet function and platelet survival.
Topics: Blood Platelets; Humans; Platelet Adhesiveness; Platelet Glycoprotein GPIb-IX Complex; Proteolysis
PubMed: 30348652
DOI: 10.1182/blood-2018-03-742668 -
Current Opinion in Hematology Sep 2019Platelets are specialized effector cells that rapidly respond to sites of vascular injury. However, emerging data demonstrate that platelets possess diverse functions... (Review)
Review
PURPOSE OF REVIEW
Platelets are specialized effector cells that rapidly respond to sites of vascular injury. However, emerging data demonstrate that platelets possess diverse functions that also mediate inflammatory responses and neurological diseases. These functions are relevant to disease processes prevalent among older adults and likely influence susceptibility to thrombotic and inflammatory disorders.
RECENT FINDINGS
Platelet counts decrease in aged individuals whereas platelet reactivity increases. The platelet transcriptome is altered in aged individuals resulting in altered platelet function and exaggerated inflammation. Platelet signaling to monocytes in aging results in significantly more cytokines because of increased platelet-derived granzyme A. Platelet activation in aging appears to be driven, in part, because of increased reactive oxygen species and activation of the mammalian target of rapamycin pathway. Increased platelet hyperactivity in diseases is associated with aging, such cardiovascular disease and sepsis, exaggerate inflammation and thrombosis. Noncanonical functions of platelets influence the development of neurological diseases including Alzheimer's disease.
SUMMARY
Although there have been advances dissecting the molecular mechanisms regarding aging-related changes in platelets, many knowledge gaps still remain. Studies filling these gaps are likely to identify new mechanisms driving aging-related changes in platelet gene expression and function, and contributing to injurious thrombo-inflammation in older adults.
Topics: Aging; Blood Platelets; Humans
PubMed: 31348047
DOI: 10.1097/MOH.0000000000000526 -
Blood Jun 2021Until recently, the nucleic acid content of platelets was considered to be fully determined by their progenitor megakaryocyte. However, it is now well understood that... (Review)
Review
Until recently, the nucleic acid content of platelets was considered to be fully determined by their progenitor megakaryocyte. However, it is now well understood that additional mediators (eg, cancer cells) can intervene, thereby influencing the RNA repertoire of platelets. Platelets are highly dynamic cells that are able to communicate and influence their environment. For instance, platelets have been involved in various steps of cancer development and progression by supporting tumor growth, survival, and dissemination. Cancer cells can directly and/or indirectly influence platelet RNA content, resulting in tumor-mediated "education" of platelets. Alterations in the tumor-educated platelet RNA profile have been described as a novel source of potential biomarkers. Individual platelet RNA biomarkers as well as complex RNA signatures may be used for early detection of cancer and treatment monitoring. Here, we review the RNA transfer occurring between cancer cells and platelets. We explore the potential use of platelet RNA biomarkers as a liquid biopsy biosource and discuss methods to evaluate the transcriptomic content of platelets.
Topics: Biomarkers, Tumor; Blood Platelets; Cell Communication; Humans; Neoplasms; RNA, Neoplasm; RNA, Transfer
PubMed: 33940602
DOI: 10.1182/blood.2019003978 -
Arteriosclerosis, Thrombosis, and... Nov 2021Myeloproliferative neoplasms (MPNs) are a group of malignant disorders of the bone marrow where a dysregulated balance between proliferation and differentiation gives... (Review)
Review
Myeloproliferative neoplasms (MPNs) are a group of malignant disorders of the bone marrow where a dysregulated balance between proliferation and differentiation gives rise to abnormal numbers of mature blood cells. MPNs encompass a spectrum of disease entities with progressively more severe clinical features, including complications with thrombosis and hemostasis and an increased propensity for transformation to acute myeloid leukemia. There is an unmet clinical need for markers of disease progression. Our understanding of the precise mechanisms that influence pathogenesis and disease progression has been limited by access to disease-specific cells as biosources. Here, we review the landscape of MPN pathology and present blood platelets as potential candidates for disease-specific understanding. We conclude with our recent work discovering progressive platelet heterogeneity by subtype in a large clinical cohort of patients with MPN.
Topics: Animals; Antineoplastic Agents; Blood Coagulation; Blood Platelets; Humans; Molecular Targeted Therapy; Myeloproliferative Disorders; Phenotype; Platelet Activation; Platelet Aggregation Inhibitors; Thrombopoiesis
PubMed: 34615371
DOI: 10.1161/ATVBAHA.121.316373