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Trends in Molecular Medicine Nov 2023Sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) is a large extracellular matrix protein that is also detected in circulation. Recent... (Review)
Review
Sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) is a large extracellular matrix protein that is also detected in circulation. Recent plasma proteomic and genomic studies have revealed a large number of associations between SVEP1 and human traits, particularly chronic disease. These include associations with cardiac death and disease, diabetes, platelet traits, glaucoma, dementia, and aging; many of these are causal. Animal models demonstrate that SVEP1 is critical in vascular development and disease, but its molecular and cellular mechanisms remain poorly defined. Future studies should aim to characterize these mechanisms and determine the diagnostic, prognostic, and therapeutic value of measuring or intervening on this enigmatic protein.
Topics: Animals; Humans; Cell Adhesion Molecules; Proteomics; Blood Platelets; Phenotype
PubMed: 37673700
DOI: 10.1016/j.molmed.2023.08.002 -
Cytometry. Part a : the Journal of the... Dec 2023Using spectral flow cytometry, we developed a 16-color panel for analysis of platelet phenotype and function in human whole blood. The panel contains markers of clinical...
Using spectral flow cytometry, we developed a 16-color panel for analysis of platelet phenotype and function in human whole blood. The panel contains markers of clinical relevance and follows an optimized protocol for the high-parameter phenotyping of (phosphatidylserine positive) procoagulant platelets. Inclusion of established markers, such as CD62P and PAC-1, allows the subsetting of classic (proinflammatory and proaggregatory) phenotypes, while addition of novel markers, such as TLR9, allows the resolution of platelets with nonclassic functions. Multiple inducible (C3b, CD63, CD107a, CD154, and TLT-1) and constitutive (CD29, CD31, CD32, CD36, CD42a, CD61, and GPVI) markers are also measurable, and we demonstrate the use of automatic gating for platelet analysis. The panel is widely applicable to research and clinical settings and can be readily modified, should users wish to tailor the panel to more specific needs.
Topics: Humans; Flow Cytometry; Blood Platelets; CD40 Ligand; Platelet Activation
PubMed: 37786346
DOI: 10.1002/cyto.a.24797 -
Journal of Internal Medicine Jul 2024Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet-hyperlipidaemia interplay and its... (Review)
Review
Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet-hyperlipidaemia interplay and its impact on atherogenesis. Native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) are the key proatherosclerotic components of hyperlipidaemia. nLDL binds to the platelet-specific LDL receptor (LDLR) ApoE-R2', whereas oxLDL binds to the platelet-expressed scavenger receptor CD36, lectin-type oxidized LDLR 1 and scavenger receptor class A 1. Ligation of nLDL/oxLDL induces mild platelet activation and may prime platelets for other platelet agonists. Platelets, in turn, can modulate lipoprotein metabolisms. Platelets contribute to LDL oxidation by enhancing the production of reactive oxygen species and LDLR degradation via proprotein convertase subtilisin/kexin type 9 release. Platelet-released platelet factor 4 and transforming growth factor β modulate LDL uptake and foam cell formation. Thus, platelet dysfunction and hyperlipidaemia work in concert to aggravate atherogenesis. Hypolipidemic drugs modulate platelet function, whereas antiplatelet drugs influence lipid metabolism. The research prospects of the platelet-hyperlipidaemia interplay in atherosclerosis are also discussed.
Topics: Humans; Atherosclerosis; Hyperlipidemias; Blood Platelets; Lipoproteins, LDL; Platelet Activation; Receptors, LDL; Hypolipidemic Agents
PubMed: 38704820
DOI: 10.1111/joim.13794 -
Seminars in Thrombosis and Hemostasis Mar 2024CD36 (also known as platelet glycoprotein IV) is expressed by a variety of different cell entities, where it possesses functions as a signaling receptor, but... (Review)
Review
CD36 (also known as platelet glycoprotein IV) is expressed by a variety of different cell entities, where it possesses functions as a signaling receptor, but additionally acts as a transporter for long-chain fatty acids. This dual function of CD36 has been investigated for its relevance in immune and nonimmune cells. Although CD36 was first identified on platelets, the understanding of the role of CD36 in platelet biology remained scarce for decades. In the past few years, several discoveries have shed a new light on the CD36 signaling activity in platelets. Notably, CD36 has been recognized as a sensor for oxidized low-density lipoproteins in the circulation that mitigates the threshold for platelet activation under conditions of dyslipidemia. Thus, platelet CD36 transduces atherogenic lipid stress into an increased risk for thrombosis, myocardial infarction, and stroke. The underlying pathways that are affected by CD36 are the inhibition of cyclic nucleotide signaling pathways and simultaneously the induction of activatory signaling events. Furthermore, thrombospondin-1 secreted by activated platelets binds to CD36 and furthers paracrine platelet activation. CD36 also serves as a binding hub for different coagulation factors and, thus, contributes to the plasmatic coagulation cascade. This review provides a comprehensive overview of the recent findings on platelet CD36 and presents CD36 as a relevant target for the prevention of thrombotic events for dyslipidemic individuals with an elevated risk for thrombosis.
Topics: Humans; CD36 Antigens; Blood Platelets; Platelet Activation; Thrombosis; Biology
PubMed: 37192651
DOI: 10.1055/s-0043-1768935 -
Circulation Research Oct 2023Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence...
BACKGROUND
Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence and underlying mechanisms remain largely unknown, and a device-related role of ECMO in thrombocytopenia has been hypothesized. This study aims to investigate the mechanisms underlying thrombocytopenia in ECMO patients.
METHODS
In a prospective cohort of 107 ECMO patients, we investigated platelet count, functions, and glycoprotein shedding. In an ex vivo mock circulatory ECMO loop, we assessed platelet responses and VWF (von Willebrand factor)-GP Ibα (glycoprotein Ibα) interactions at low- and high-flow rates, in the presence or absence of red blood cells. The clearance of human platelets subjected or not to ex vivo perfusion was studied using an in vivo transfusion model in NOD/SCID (nonobese diabetic/severe combined Immunodeficient) mice.
RESULTS
In ECMO patients, we observed a time-dependent decrease in platelet count starting 1 hour after device onset, with a mean drop of 7%, 35%, and 41% at 1, 24, and 48 hours post-ECMO initiation (=0.00013, <0.0001, and <0.0001, respectively), regardless of the type of ECMO. This drop in platelet count was associated with a decrease in platelet GP Ibα expression (before: 47.8±9.1 versus 24 hours post-ECMO: 42.3±8.9 mean fluorescence intensity; =0.002) and an increase in soluble GP Ibα plasma levels (before: 5.6±3.3 versus 24 hours post-ECMO: 10.8±4.1 µg/mL; <0.0001). GP Ibα shedding was also observed ex vivo and was unaffected by (1) red blood cells, (2) the coagulation potential, (3) an antibody blocking VWF-GP Ibα interaction, (4) an antibody limiting VWF degradation, and (5) supraphysiological VWF plasma concentrations. In contrast, GP Ibα shedding was dependent on rheological conditions, with a 2.8-fold increase at high- versus low-flow rates. Platelets perfused at high-flow rates before being transfused to immunodeficient mice were eliminated faster in vivo with an accelerated clearance of GP Ibα-negative versus GP Ibα-positive platelets.
CONCLUSIONS
ECMO-associated shear forces induce GP Ibα shedding and thrombocytopenia due to faster clearance of GP Ibα-negative platelets. Inhibiting GP Ibα shedding could represent an approach to reduce thrombocytopenia during ECMO.
Topics: Humans; Animals; Mice; von Willebrand Factor; Prospective Studies; Mice, Inbred NOD; Mice, SCID; Blood Platelets; Thrombocytopenia
PubMed: 37883587
DOI: 10.1161/CIRCRESAHA.123.322752 -
Zhonghua Jie He He Hu Xi Za Zhi =... Feb 2024Platelets are important cells in hemostatic and coagulative reactions. Interestingly, platelets-related immunopathological mechanism and clinical research have become... (Review)
Review
Platelets are important cells in hemostatic and coagulative reactions. Interestingly, platelets-related immunopathological mechanism and clinical research have become one of the hot research topics in tuberculosis at home and abroad in recent years. Platelets get involved in host chronic inflammation and pulmonary immune response, thus playing a negative regulatory role in tuberculosis. This is achieved through direct internalization of and indirect interaction with immune cells. In addition, patients with tuberculosis often have thrombocytosis, and there is increasing evidence that anti-platelet therapy as a host-directed therapy has demonstrable clinical benefit in tuberculosis control. Platelet inhibition may be an emerging therapeutic strategy for tuberculosis. This review aims to highlight the research progress in platelets and tuberculosis.
Topics: Humans; Tuberculosis; Mycobacterium tuberculosis; Blood Platelets; Lung
PubMed: 38309972
DOI: 10.3760/cma.j.cn112147-20230831-00121 -
Thrombosis Research Nov 2023Platelets are anucleated cells produced by megakaryocytes, from which they inherit all the components necessary to carry their functions. They circulate in blood vessels... (Review)
Review
Platelets are anucleated cells produced by megakaryocytes, from which they inherit all the components necessary to carry their functions. They circulate in blood vessels where they play essential roles in coagulation, wound repair or inflammation, and have been implicated in various pathological conditions such as thrombosis, viral infection or cancer progression. The importance of these cells has been established over a century ago, and effective anti-platelet medications with different mechanisms of action have since been developed. However, these therapies are not always effective and can incur adverse events, thus a better understanding of platelets molecular processes is needed to address these issues and improve our understanding of platelet functions. In recent years, an increasing number of studies have leveraged OMICs technologies to analyze their content and identify molecular signatures and mechanisms associated with platelet functions and platelet related disorders. In particular, the increased accessibility of microarrays and RNA sequencing opened the way for studies of the platelet transcriptome under a wide array of conditions. These studies revealed distinct expression profiles in diverse pathologies, which could lead to the discovery of novel biomarkers and therapeutic targets, and suggests a dynamic transcriptome that could influence platelet mechanisms. In this review, we highlight the different sources of transcript level variability in platelets while summarizing recent advances and discoveries from this emerging field.
Topics: Humans; Transcriptome; Blood Platelets; Megakaryocytes; Blood Coagulation; Hemostasis; Blood Platelet Disorders
PubMed: 37357099
DOI: 10.1016/j.thromres.2023.06.009 -
Annals of Medicine Dec 2023Platelet-rich plasma (PRP) has been widely used in clinical practice. The mechanism by which PRP promotes tissue repair lies in the release of multiple growth factors... (Review)
Review
Platelet-rich plasma (PRP) has been widely used in clinical practice. The mechanism by which PRP promotes tissue repair lies in the release of multiple growth factors upon platelet activation, which accelerates the proliferation and differentiation of repair cells and the synthesis of extracellular matrix. In recent years, as extracellular vesicles (EVs) research has increased and intensified, it has been found that EVs also play an important role in tissue repair. This article provides a comprehensive review of the role of PRP and PRP-derived extracellular vesicles (PRP-EVs) in tissue repair. It discusses the biological characteristics, extraction, identification, activation, and preservation of PRP-EVs. It also reviews their applications in orthopedics and wound repair. The article highlights the importance of PRP-EVs in modern medicine and suggests that they could be a promising natural nanocarrier.
Topics: Humans; Platelet-Rich Plasma; Extracellular Vesicles; Blood Platelets; Intercellular Signaling Peptides and Proteins
PubMed: 38065677
DOI: 10.1080/07853890.2023.2287705 -
International Journal of Nanomedicine 2023In addition to hemostasis and coagulation, years of studies have proved that platelets are involved in the whole process of tumor progression, including tumor invasion,... (Review)
Review
In addition to hemostasis and coagulation, years of studies have proved that platelets are involved in the whole process of tumor progression, including tumor invasion, intravasation, extravasation, and so on. It means that this property of platelets can be used in anti-tumor therapy. However, traditional platelet-based antitumor drugs often cause autologous platelet damage due to lack of targeting, resulting in serious side effects. Therefore, the researchers designed a variety of anti-tumor drug delivery systems based on platelets by targeting platelets or platelet membrane coating. The drug delivery systems have special response modes, which is crucial in the design of nanoparticles. These modes enhance the targeting and improve the anti-tumor effect. Here, we present a review of recent discoveries in the field of the crosstalk between platelets and tumors and the progress of platelet-based anti-tumor nanoparticles.
Topics: Humans; Blood Platelets; Antineoplastic Agents; Cell Membrane; Neoplasms; Drug Delivery Systems; Nanoparticles
PubMed: 37954456
DOI: 10.2147/IJN.S436373 -
Arteriosclerosis, Thrombosis, and... Aug 2023Blood flow-induced hemodynamic changes result in mechanical stress on blood cells and vessel walls. Increased shear stress can activate platelets and other circulating... (Review)
Review
Blood flow-induced hemodynamic changes result in mechanical stress on blood cells and vessel walls. Increased shear stress can activate platelets and other circulating cells, triggering the rapid activation of receptors, calcium channels, and related signaling mechanisms. Shear stress can also modify the folding of extracellular molecules and directly activate mechanosensitive receptors and calcium channels. The mechanical movement of the extracellular matrix and the intracellular cortical actin cytoskeleton can change the conformation of platelet receptors and gate channel pores in the plasma membrane. Mechanosensitive platelet receptors and their downstream signaling events and metabolic products can also indirectly activate calcium channels. While the molecular composite of mechanotransduction pathways has been described in mammals, shear stress-induced platelet receptors and their cross talk with calcium channels have been incompletely characterized. In this review, we discuss current knowledge about the role of mechanosensitive platelet receptors and calcium channels in shear-dependent platelet activation and arterial thrombus formation.
Topics: Animals; Blood Platelets; Calcium Channels; Mechanotransduction, Cellular; Platelet Activation; Signal Transduction; Calcium; Stress, Mechanical; Mammals
PubMed: 37345523
DOI: 10.1161/ATVBAHA.123.318341