-
Oncotarget Aug 2015
Topics: Blood Platelets; Humans; Signal Transduction
PubMed: 26343368
DOI: 10.18632/oncotarget.5122 -
Biochemistry. Biokhimiia Jan 2002Platelets actively participate in regulating thrombin production following physical or chemical injury to blood vessels. Injury to blood vessels initiates activation of... (Review)
Review
Platelets actively participate in regulating thrombin production following physical or chemical injury to blood vessels. Injury to blood vessels initiates activation of the large numbers of platelets that appear in the subendothelium where they become exposed to tissue factor and to molecules adhesive for platelets and normally found in the extracellular matrix. The complex of plasma factor VIIa with extravascular tissue factor both initiates and localizes thrombin production on platelets and on extravascular cells. Thrombin production at these sites in turn enhances platelet activation and the subsequent hemostatic plug formation to minimize bleeding. Thrombin production and platelet activation also initiate the process of wound healing requiring thrombin-dependent cell activation and platelet-dependent formation of new blood vessels (angiogenesis). Activated platelets release from their storage granules several proteins and other factors that regulate local thrombin formation and the responses of blood vessel cells to injury to assure hemostasis and effective wound healing. Failure to localize and adequately regulate thrombin production and/or platelet activation can have pathological consequences, including the development and propagation of atherosclerosis and enhancement of tumor development. The primary basis for the pathological consequences of the failure to adequately regulate thrombin production is that the multi-functional thrombin activates several types of cells to initiate their mitogenesis. Mitogenesis precedes many of the undesirable consequences of poorly regulated thrombin production and platelet activation. In addition, activated platelets release a variety of products which influence the functions of several cell types to the extent that inadequate regulation of platelet activation (by excessive thrombin production) could contribute to the pathogenesis of acute and chronic arterial thrombosis and to tumor development. Activated platelets participate in tumor development by releasing several factors that positively (and negatively) regulate blood vessel formation.
Topics: Blood Coagulation; Blood Platelets; Cell Adhesion; Cell Division; Cell Membrane; Cells, Cultured; Hemostasis; Humans; Neovascularization, Physiologic; Prothrombin; Thrombin; Wound Healing
PubMed: 11841339
DOI: 10.1023/a:1013948013577 -
Advances in Experimental Medicine and... 2014Platelets are small, anucleated cells that participate in primary hemostasis by forming a hemostatic plug at the site of a blood vessel's breach, preventing blood loss.... (Review)
Review
Platelets are small, anucleated cells that participate in primary hemostasis by forming a hemostatic plug at the site of a blood vessel's breach, preventing blood loss. However, hemostatic events can lead to excessive thrombosis, resulting in life-threatening strokes, emboli, or infarction. Development of multi-scale models coupling processes at several scales and running predictive model simulations on powerful computer clusters can help interdisciplinary groups of researchers to suggest and test new patient-specific treatment strategies.
Topics: Animals; Blood Coagulation; Blood Platelets; Blood Vessels; Cell Communication; Hemostasis; Humans; Platelet Activation; Platelet Adhesiveness; Systems Biology
PubMed: 25480638
DOI: 10.1007/978-1-4939-2095-2_5 -
Blood Transfusion = Trasfusione Del... Jan 2018Leucoreduction of blood components, including platelet components, is strongly encouraged but not yet universal, especially outside high income countries. As both...
BACKGROUND
Leucoreduction of blood components, including platelet components, is strongly encouraged but not yet universal, especially outside high income countries. As both leucocytes and platelets secrete copious amounts of pro-inflammatory cytokines/chemokines under various conditions and during storage, we investigated the potential of the respective secretory programmes of these cells in order to evaluate their subsequent pathophysiological effects.
MATERIAL AND METHODS
A total of 158 individual non-leucoreduced platelet components were obtained from Tunisian donors and tested for characteristic biological response modifiers (BRM) of leukocytes (IL-1β, IL-8), platelets (sCD62P, sCD40L) and both cell types (TNF-α, RANTES) in the presence or absence of thrombin stimulation and after different periods of storage (up to 5 days). BRM levels were determined using enzyme-linked immunosorbent assays and Luminex technology. Platelet-leucocyte aggregate formation during storage was analysed using flow cytometry.
RESULTS
Leucocyte- and platelet-associated BRM had clearly distinct profiles both at the onset (day 0) and termination (day 5) of the observation period but altered during the intermediate period so that their respective importance was inverted; in fact, the profiles were merged and indistinguishable on days 2-3. The leucocyte-derived BRM largely dominated over platelet-derived ones and further altered the BRM platelet secretion programme.
DISCUSSION
This study contributes substantial, new information on leucocyte/platelet interactions and their likely role in transfusion when leucodepletion cannot be performed or is only partially achieved.
Topics: Blood Platelets; Blood Preservation; Cytokines; Female; Humans; Leukocytes; Male; Time Factors
PubMed: 27643752
DOI: 10.2450/2016.0076-16 -
International Journal of Hematology Apr 2012Inorganic polyphosphate (polyP) is abundant in biological organisms. PolyP is a major component of dense granules of human platelets and is secreted upon platelet... (Review)
Review
Inorganic polyphosphate (polyP) is abundant in biological organisms. PolyP is a major component of dense granules of human platelets and is secreted upon platelet activation. Studies from our lab and others have shown that polyP is a potent modulator of the blood clotting cascade, acting as a pro-hemostatic, prothrombotic and proinflammatory agent depending on its polymer size and location. PolyP may represent at least one of the long-sought (patho)physiologic activators of the contact pathway of blood clotting, and its actions may also help to explain previously unexplained abilities of activated platelets to enhance plasma clotting reactions. PolyP may have utility as a hemostatic agent to control bleeding, and conversely, polyP antagonists might have utility as antithrombotic/anti-inflammatory agents with reduced bleeding side effects. The detailed molecular mechanisms by which polyP modulates blood clotting reactions still remain to be elucidated.
Topics: Animals; Blood Coagulation; Blood Platelets; Humans; Inflammation; Platelet Activation; Polyphosphates; Thrombosis
PubMed: 22477540
DOI: 10.1007/s12185-012-1054-5 -
Acta Biomaterialia Jun 2019Elevated shear force caused by an anastomotic stenosis is a common complication at the blood vessel-vascular implant interface. Although elevated shear forces were found...
Elevated shear force caused by an anastomotic stenosis is a common complication at the blood vessel-vascular implant interface. Although elevated shear forces were found to cause platelet aggregation around a stenotic region, transient platelet exposure to elevated shear forces and subsequent downstream events occurring under lower shear force were not extensively studied. We hypothesize that effects of elevated shear forces on pre-activation of platelets for downstream adhesion and activation are relevant in understanding the increased thrombotic risk associated with blood-contacting devices. We designed a microfluidic flow system to mimic the hemodynamic environment of vasculature with an upstream anastomotic stenosis with five wall shear strain rates ranging from 1620 s to 11560 s. Under shear flow conditions, transient exposure of whole blood to elevated shear forces resulted in higher downstream platelet adhesion onto three different immobilized platelet agonists: fibrinogen, collagen, or von Willebrand factor. Platelet expression of four activation markers (P-selectin, GPIIb/IIIa, lysosomal glycoprotein, and phosphatidylserine) significantly increased after transient exposure to higher upstream wall shear strain rates of 2975-11560 s. A significant lysis was observed when platelets were primed by upstream wall shear strain rate of 11560 s. These experimental results could be helpful to understand how altered hemodynamics around an anastomotic stenosis promotes thrombus formation downstream. STATEMENT OF SIGNIFICANCE: Studying the downstream response of platelets following transient exposure to an upstream agonist is important because of significant clinical implications to the implantation of vascular devices. Due to intimal fibrous hyperplasia, vascular biomaterials such as synthetic small-diameter vascular grafts sometimes become stenotic (narrow), leading to transient platelet exposure to elevated shear forces. In this study, a microfluidic flow system was developed to mimic a stenosed vascular graft and to investigate how highly elevated, transient upstream shear forces, typically found in severe stenosis, results in the pre-activation of platelets for downstream adhesion and activation. The findings of the present study have implications for optimizing the design of blood-contacting biomaterials in order to minimize thrombotic risk associated with transiently elevated shear forces. The findings also provide additional insights into the mechanisms of thrombus formation at the post-stenotic regions of vascular implants.
Topics: Blood Platelets; Constriction, Pathologic; Flow Cytometry; Humans; Models, Cardiovascular; Platelet Adhesiveness; Shear Strength
PubMed: 31004847
DOI: 10.1016/j.actbio.2019.04.028 -
Thrombosis Research Apr 2014Platelets interact with the endothelium to regulate vascular integrity and barrier function, mediate inflammation and immune response, and prevent and arrest hemorrhage.... (Review)
Review
Platelets interact with the endothelium to regulate vascular integrity and barrier function, mediate inflammation and immune response, and prevent and arrest hemorrhage. In this review, we describe existing tools to study the flow-dependent interactions of platelets with the vessel wall. We also discuss our work on building engineered microvessels to study the roles of platelets on endothelial barrier function, endothelial sprouting, and thrombus formation on both quiescent and stimulated endothelium. In particular, we will show the advantage of using a cell-remodelable system in the studies of platelet-vessel wall interactions.
Topics: Animals; Blood Platelets; Endothelial Cells; Endothelium; Humans
PubMed: 24438943
DOI: 10.1016/j.thromres.2013.12.039 -
International Review of Cytology 2002The human blood platelet circulates in the blood as a non-adherent disk. Upon receiving signals of blood vessel damage, the platelet reorganizes its actin cytoskeleton... (Review)
Review
The human blood platelet circulates in the blood as a non-adherent disk. Upon receiving signals of blood vessel damage, the platelet reorganizes its actin cytoskeleton which transforms it into a spiky dynamic adherent glue. This transformation involves a temporal sequence of four morphologically distinct steps which is reproducible in vitro. The actin dynamics underlying these shape changes depend on a large number of actin-binding proteins. Maintenance of the discoid shape requires actin-binding proteins that inhibit these reorganizations, whereas transformation involves other proteins, some to disassemble old filaments and others to polymerize new ones. F-Actin-affinity chromatography identified a large set of actin-binding proteins including VASP, Arp2 and 2E4/kaptin. Recent discoveries show that VASP inhibits filament disassembly and Arp2/3 is required to polymerize new filaments. Morphological analysis of the distribution of these actin-binding proteins in spread platelets together with biochemical measurements of their interactions with actin lead to a model of interactions with actin that mediate shape change.
Topics: Actins; Animals; Blood Platelets; Calcium; Cytoplasm; Humans; Platelet Activation; Time Factors
PubMed: 12019562
DOI: 10.1016/s0074-7696(02)17014-8 -
Journal of Biomedical Science Apr 2010While there have been many reports investigating the biological activity and signaling mechanisms of isoprostanes, their role in biology, particularly in platelets,... (Review)
Review
While there have been many reports investigating the biological activity and signaling mechanisms of isoprostanes, their role in biology, particularly in platelets, appears to still be underestimated. Moreover, whether these lipids have their own receptors is still debated, despite multiple reports that discrete receptors for isoprostane do exist on platelets, vascular tissues, amongst others. This paper provides a review of the important literature of isoprostanes and provides reasoning that isoprostanes should be classified as orphan ligands until their receptor(s) is/are identified.
Topics: Arachidonic Acid; Blood Platelets; Hemostasis; Humans; Isoprostanes; Models, Molecular; Molecular Structure; Platelet Activation; Signal Transduction
PubMed: 20370921
DOI: 10.1186/1423-0127-17-24 -
Blood Sep 2004The major platelet integrin, alphaIIbbeta3, is required for platelet interactions with proteins in plasma and the extracellular matrices (ECMs) that are essential for... (Review)
Review
The major platelet integrin, alphaIIbbeta3, is required for platelet interactions with proteins in plasma and the extracellular matrices (ECMs) that are essential for platelet adhesion and aggregation during hemo stasis and arterial thrombosis. Lig and binding to alphaIIbbeta3 is controlled by inside-out signals that modulate receptor conformation and clustering. In turn, ligand binding triggers outside-in signals through alphaIIbbeta3 that, when disrupted, can cause a bleeding diathesis. In the past 5 years there has been an explosion of knowledge about the structure and function ofalphaIIbbeta3 and the related integrin, alphaVbeta3. These developments are discussed here, and current models of bidirectional alphaIIbbeta3 signaling are presented as frameworks for future investigations. An understanding that alphaIIbbeta3 functions as a dynamic molecular scaffold for extracellular and intracellular proteins has translated into diagnostic and therapeutic insights relevant to hematology and cardiovascular medicine, and further advances can be anticipated.
Topics: Animals; Blood Platelets; Humans; Integrins; Platelet Adhesiveness; Protein Binding; Signal Transduction
PubMed: 15205259
DOI: 10.1182/blood-2004-04-1257