• In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation. (wikipedia.org)
  • Thus, modulation of platelet aggregation and coagulation pathways represents the main therapeutical strategy pursued in the management of thrombotic disorders 4 . (nature.com)
  • Platelet activation and aggregation are complex processes that depend on a variety of factors, including local blood flow conditions and the surrounding biochemical environment. (frontiersin.org)
  • To overcome this limitation, we developed a fully three-dimensional multiscale model for platelet aggregation under flow and validated model predictions against experimental observations in prior work [ 9 ]. (frontiersin.org)
  • Human platelets were loaded with aequorin, a Ca2(+)-sensitive photoprotein, and tested in the platelet-ionized calcium aggregometer for simultaneous recording of platelet aggregation and intraplatelet Ca2+ levels both in the presence and in the absence of autologous polymorphonuclear leukocytes. (nih.gov)
  • Amplification of both platelet aggregation and intraplatelet Ca2+ movement was induced by PAF in the presence of leukocytes. (nih.gov)
  • Cell-free supernatants prepared from FMLP-stimulated leukocytes were able to induce platelet aggregation, thromboxane B2 generation, and Ca2+ mobilization, although at a reduced degree as compared with intact leukocyte addition. (nih.gov)
  • Platelet aggregation, granule secretion and platelet-leukocyte interaction were analyzed by lumi-aggregometry and flow cytometry. (elifesciences.org)
  • Strikingly, prevention of DLL-4-Notch1 interaction by a blocking antibody abolished platelet aggregation and extracellular vesicle shedding induced by thrombin. (elifesciences.org)
  • After stimulation with LPA and thrombin under conditions, where platelet aggregation could not occur, the kinetics of cofilin de- and rephosphorylation were unperturbed indicating their independence of integrin IIbβ3 engagement. (uni-muenchen.de)
  • Since the kinetics of cofilin phospho-cycle was similar during secretion and platelet aggregation in LPA- and thrombin-stimulated cells, I propose a general two-step regulatory process for cofilin phospho-cycle underlying primarily secretion, and subsequently platelet aggregation: dephosphorylation by a cofilin phosphatase and then rephosphorylation by the Rho-kinase/LIMK-1 pathway. (uni-muenchen.de)
  • However, diabetic patients have significantly higher platelet aggregation and activation than non-diabetic patients, including those undergoing dual antiplatelet therapy [ 4 - 6 ]. (aging-us.com)
  • However, the ultimate common pathway of platelet aggregation is the activation of glycoprotein (GP) IIb/IIIa receptors present on platelet surface [ 7 - 9 ]. (aging-us.com)
  • The primary endpoint was assessment of platelet aggregation after stimulation with adenosine diphosphate 20 μM at 12-month follow-up. (revespcardiol.org)
  • In our previous study, several compounds extracted from this herb, including luteolin‑4'‑O‑β‑D‑glucopyranoside (LGP), were revealed to exert inhibitory effects on adenosine diphosphate (ADP)‑induced platelet aggregation. (spandidos-publications.com)
  • Using a platelet‑aggregation assay, it was revealed that LGP significantly inhibited platelet aggregation induced by ADP, U46619 and arachidonic acid. (spandidos-publications.com)
  • In conclusion, the data presented here demonstrated that LGP, a natural compound from C. nudiflora Hook, inhibited the development of platelet aggregation and amplification of platelet activation. (spandidos-publications.com)
  • Upon vascular injury, platelets are exposed to the subendothelium, and several agonists, including adenosine diphosphate (ADP) and thrombin, are generated at the injury site, which can stimulate platelet adhesion, activation and aggregation. (spandidos-publications.com)
  • The uncontrolled progression of these processes through a series of self-sustaining amplification loops can initiate unrestrained platelet activation and aggregation, and eventually lead to thromboembolic events ( 7 , 8 ). (spandidos-publications.com)
  • It has been demonstrated clinically that the use of antiplatelet agents to prevent and/or reverse platelet aggregation is a successful strategy for the prevention of thrombosis ( 7 , 8 ). (spandidos-publications.com)
  • Platelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study. (tmu.edu.tw)
  • Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca2+]i mobilization. (tmu.edu.tw)
  • Conclusions: Sesamol activates cAMP-PKA signaling, followed by inhibition of the NF-B-PLC-PKC cascade, thereby leading to inhibition of [Ca2+]i mobilization and platelet aggregation. (tmu.edu.tw)
  • Prostacyclin is a strong vasodilator of all vascular beds and a potent endogenous inhibitor of platelet aggregation. (medscape.com)
  • Prostacyclin may decrease thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation. (medscape.com)
  • It elicits direct vasodilation of pulmonary and systemic arterial vessels and inhibits platelet aggregation. (medscape.com)
  • Integrin-mediated interactions with the extracellular matrix (ECM) are required for the attachment, cytoskeletal organization, mechanosensing, migration, proliferation, differentiation and survival of cells in the context of a multitude of biological processes including fertilization, implantation and embryonic development, immune response, bone resorption and platelet aggregation. (thno.org)
  • Figure 1 demonstrates different steps of platelet tethering, adhesion, aggregation and thrombus formation. (biomedcentral.com)
  • 70%. Severe cases exhibit abnormal coagulation, endothelial barrier disruption, and dysfunctional platelet aggregation but the underlying mechanisms remain poorly understood. (cdc.gov)
  • Phosphorylation of this tyrosine initiates binding of spleen tyrosine kinase (Syk) and triggers further downstream signaling events and ultimately potent platelet activation and aggregation. (ox.ac.uk)
  • Various mechanisms, including endothelial cell nitric oxide and prostacyclin, promote blood fluidity by preventing platelet aggregation and dilating intact blood vessels. (msdmanuals.com)
  • During activation, platelets release mediators of aggregation, including adenosine diphosphate (ADP) from storage granules. (msdmanuals.com)
  • ADP, thromboxane A2, and other mediators induce activation and aggregation of additional platelets on the injured endothelium. (msdmanuals.com)
  • Another reported type of leukocyte adhesion deficiency involves dysfunction in platelet aggregation in addition to a defect in leukocyte adhesion. (medscape.com)
  • Do Blood Platelets Affect Quality of Organs to be Transplanted from a Brain-Dead Organ Donor? (rotrf.org)
  • This project aims to investigate whether part of the organ damage in the brain-dead organ donor can be explained by adhesion of blood platelets to the activated endothelium. (rotrf.org)
  • The mechanism of early activation of GP IIb/IIIa receptors in diabetic conditions remains unknown. (aging-us.com)
  • In conclusion, EMP-PDI promotes early platelet activation through glycoprotein (GP) IIb/IIIa receptors present on platelet surface in the diabetic state. (aging-us.com)
  • The identification of the key molecules that accurately regulate the activation of these receptors may provide a novel approach for antiplatelet therapy. (aging-us.com)
  • Receptors that are tyrosine protein kinases include those receptors for platelet-derived growth factor (PDGF), insulin, epidermal growth factor (EGF) and certain lymphokines. (discoverx.com)
  • Physiologically, upon platelet activation, uncontrolled propagation of thrombosis is prevented by regulating mechanisms which affect the expression and function of either platelet adhesion receptors or integrins. (biomedcentral.com)
  • Alternatively, further activation of platelets is associated with microvesiculation as a none-selective mechanism which leads to the loss of membrane- bearing receptors. (biomedcentral.com)
  • In a non-physiological condition, the storage of therapeutic platelets has also shown to be associated with the unwilling activation of platelets which triggers receptors down-regulation via aforementioned different mechanisms. (biomedcentral.com)
  • While the expression and shedding of pro-inflammatory molecules can induce post-transfusion adverse effects, stored-dependent loss of adhesion receptors by ectodomain shedding or microvesiculation may attenuate post-transfusion adhesive functions of platelets causing their premature clearance from circulation. (biomedcentral.com)
  • In its first part, the review presented here aims to describe the mechanisms involved in down-regulation of platelet adhesion receptors. (biomedcentral.com)
  • Platelets firmly adhere to the sub-endothelial matrix through the engagement of collagen receptors α2β1 and GPVI (Adhesion) . (biomedcentral.com)
  • Background Activation of human platelets with thrombin proceeds via two protease-activated receptors (PARs), PAR1 and PAR4, that have identical main intracellular signaling responses. (ipmnet.ru)
  • VWF binds to receptors on the platelet surface membrane (glycoprotein Ib/IX). (msdmanuals.com)
  • Platelet receptors for ADP include the P2Y12 receptor, which sends signals to suppress adenylate cyclase, decreases cyclic adenosine monophosphate (cAMP) levels, and promotes activation of the glycoprotein IIb/IIIa receptor (assembled on the activated platelet surface membrane from glycoproteins IIb and IIIa). (msdmanuals.com)
  • Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. (bvsalud.org)
  • Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types. (bvsalud.org)
  • Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide. (nature.com)
  • DLL-4, in turn, instigated neighbouring platelets to switch to 'activated' phenotype through cleavage of Notch receptor and release of its intracellular domain (NICD), which was averted by inhibition of γ-secretase and phosphatidylinositol-3-kinase (PI3K). (elifesciences.org)
  • Qin R , Zhu H , Wang F , Song M , Lin P , Xing Y , Zhang W , Zhong M , Wang Z , . Platelet activation in diabetic mice models: the role of vascular endothelial cell-derived protein disulfide isomerase-mediated GP IIb/IIIa receptor activation. (aging-us.com)
  • GP IIb/IIIa receptor activation plays an important role in thrombosis. (aging-us.com)
  • Recent evidence obtained in mouse models shows its essential role regulating blood cell function through various mechanisms that include pseudohypoxia responses by hypoxia-inducible factor-1α activation, post-translational modifications like succinylation, and communication mediated by succinate receptor 1. (haematologica.org)
  • Receptor tyrosine kinases are cell surface transmembrane proteins responsible for intracellular signal transduction. (discoverx.com)
  • Inhibition of PDGFRB (PDGFR1, JTK12, CD140B,Beta platelet-derived growth factor) receptor kinase may be useful in the treatment of several tumors. (discoverx.com)
  • Inflammatory conditions (e.g., allergy, asthma, and autoimmune diseases) have long been thought to be mainly mediated by the activation of histamine receptor 1 (H1R). (hindawi.com)
  • A general overview of the immune cascades triggered by histamine receptor activation is provided. (hindawi.com)
  • PrP(10626)-induced rise in intracellular absolutely free calcium in platelets was identified to involve transient receptor probable channel (TRPC) proteins 4. (cathepsin-s.com)
  • Apoptosis was determined by flow cytometry analysis through FITC-annexin V binding to platelet membrane PS exposed under basal conditions and after stimulation with a PAR-1 receptor agonist (TRAP, SFLLRN, thrombin receptor-activating peptide 6). (ashpublications.org)
  • Platelet activation was determined through FITC-fibrinogen, FITC-PAC-1 (a mAb that recognizes activated conformation of fibrinogen receptor) and FITC-P-selectin mAb binding to quiescent and 100 mM TRAP activated platelets by flow cytometry. (ashpublications.org)
  • Integrins are not constitutively active but rather exist in multiple activation states wherein ligand binding stability is related to the activation status of the receptor. (thno.org)
  • An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ . (nih.gov)
  • Methods We developed a multicompartmental stochastic computational systems biology model of dual-receptor thrombin signaling in platelets to gain insight into the mechanisms and roles of PAR1 and PAR4 functioning. (ipmnet.ru)
  • The platelet receptor CLEC-2 is active as a dimer. (ox.ac.uk)
  • The platelet receptor CLEC-2 binds to the snake venom toxin rhodocytin and the tumor cell surface protein podoplanin. (ox.ac.uk)
  • Platelet-derived extracellular vesicles were documented with Nanoparticle Tracking Analyzer. (elifesciences.org)
  • Sphingosine-1-phosphate (SPP) is a novel lipid messenger with both intracellular and extracellular functions. (novusbio.com)
  • Sustained calcium signalling in lymphocytes and platelets requires the uptake of extracellular calcium when intracellular stores are depleted. (reactome.org)
  • T-helper cells (CD4 + ) play a critical immune role by activating our B-cell antibody production in response to extracellular pathogens and activating our macrophages in response to intracellular pathogens. (lifeextension.com)
  • In the absence of extracellular Na + , the platelets were acidified to the same extent with AFC or with ethanol (control): 6.530 ± 0.031 versus 6.532 ± 0.031 (P = 0.97). (elsevierpure.com)
  • Extracellular factors that influence integrin activation are ligand binding, divalent cation concentration, chemokine signaling and mechanical stress. (thno.org)
  • We demonstrate expression of Notch1, its ligand DLL-4 and their respective transcripts in human platelets. (elifesciences.org)
  • Experiments were conducted using human platelets and N-acetyl-S-trans,trans-farnesyl-L cysteine (AFC), a specific prenylcysteine methyltransferase inhibitor. (elsevierpure.com)
  • Our data indicate that inhibition of carboxyl methylation reduces basal pH(i) and alters the kinetic properties of the Na + -H + antiporter in human platelets, suggesting that carboxyl methylation is implicated in the regulation of intracellular pH homeostasis. (elsevierpure.com)
  • Experiments employing continuous flow cytometry of washed human platelets were used to validate the model and test its predictions. (ipmnet.ru)
  • Platelet-activating factor (PAF) stimulates human B cells, resulting in elevation of intracellular calcium and the release of inositol phosphates. (jci.org)
  • Intracellular calcium was monitored by fluorescence spectrophotometry. (elifesciences.org)
  • In exocrine acinar cells regulation of intracellular calcium plays a pivotal role in controlling fluid and protein secretion. (rochester.edu)
  • Exposure of cells to neurotransmitters and hormones results in a rapid elevation of intracellular calcium. (rochester.edu)
  • The process whereby intracellular calcium depletion stimulates calcium uptake is often referred to as Store-operated calcium entry (SOCE). (reactome.org)
  • Spectrofluorometric measurement of intracellular free calcium 5. (cathepsin-s.com)
  • PrP(10626) induces rise in intracellular no cost calcium in platelets three. (cathepsin-s.com)
  • Platelets are anucleate cytoplasmic fragments, deriving from precursor megakaryocytes, which play key roles in processes such as thrombosis, hemostasis, inflammation, wound healing and angiogenesis. (nature.com)
  • Overall, the parallelized multiscale framework described here is demonstrated to be a promising approach for studying single-platelet resolved thrombosis at length scales that are sufficiently large to directly simulate coronary blood vessels. (frontiersin.org)
  • Platelets are the primary cellular components involved in arterial thrombosis. (frontiersin.org)
  • We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. (nih.gov)
  • Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. (nih.gov)
  • Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk. (nih.gov)
  • Inhibition of Notch signaling, too, restrained agonist-induced platelet activation, and significantly impaired arterial thrombosis in mice. (elifesciences.org)
  • In thrombosis, platelet activation serves as the initiation factor. (aging-us.com)
  • Platelets are small, a nucleate blood cells, the major role of which is in hemostasis and thrombosis owing to their capacity to adhere to damaged blood vessels and to accumulate at sites of injury ( 1 ). (spandidos-publications.com)
  • S. Whiteheart University of Kentucky, Lexington, Usa Background: Platelets use SNARE-mediated exocytosis to sustain hemostasis and thrombosis. (cathepsin-s.com)
  • These processes are maintained through the exocytosis of platelet releasate through the 3 forms of granules in platelets: dense, alpha, and lysosomal. (cathepsin-s.com)
  • More western blotting experiments demonstrated the presence on the -synuclein-interactor Cysteine String Protein, extra a brand new component for the regarded platelet secretory machinery (Figure two). (cathepsin-s.com)
  • This inflammatory state is accompanied by activation of endothelial cells, which express adhesion molecules, and release contents of their intracellular granules. (rotrf.org)
  • The results of this study will teach us whether quality of organs used for transplantation can be improved by prevention of platelet adhesion to the activated graft endothelium. (rotrf.org)
  • The firm adhesion of platelets to the site of injury forms a monolayer which serves as a reactive site for further recruitment of free-flowing platelets. (biomedcentral.com)
  • a Different Stages of Platelet Adhesion to the Site of Vascular Injury. (biomedcentral.com)
  • Initial platelet adhesion is to long strings of von Willebrand factor (VWF) that have been previously secreted by, and anchored to, stimulated endothelial cells. (msdmanuals.com)
  • Inhibition of the Rho-kinase/LIMK-1 pathway unmasked cofilin dephosphorylation suggesting that during shape change the simultaneous activation of a cofilin phosphatase counteracts the effect of LIMK-1 for phosphorylating cofilin. (uni-muenchen.de)
  • Therefore, understanding the molecular mechanisms of platelet activation and identifying novel techniques for platelet inhibition remain critically important. (spandidos-publications.com)
  • Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data demonstrating that inhibition of NF-B interferes with platelet function may have a great impact when these types of drugs are considered for the treatment of cancer and various inflammatory diseases. (tmu.edu.tw)
  • Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. (nature.com)
  • describes a novel signaling pathway involving Notch1 and its ligand, Δ-like ligand-4 (DLL4) in driving platelet activation and thrombus formation. (elifesciences.org)
  • The activation of platelets is a central step during the physiological process of hemostasis and its understanding may lead us to control the pathophysiological process of intra-arterial thrombus formation and vascular occlusion, which can cause acute coronary syndrome and myocardial infarction. (uni-muenchen.de)
  • Platelet activation and subsequent accumulation at sites of vascular injury are central to thrombus formation, which is considered to be a trigger of several cardiovascular diseases. (spandidos-publications.com)
  • Nonetheless, physiological thrombus formation (mural thrombi) is tightly regulated to avoid excessive platelet accumulation at the injury site and vascular obstruction, the principal pathological process causing heart attacks and ischaemic stroke [ 5 ]. (biomedcentral.com)
  • The activation of Rho-kinase was found to be upstream to secretion and integrin IIbβ3 activation. (uni-muenchen.de)
  • The rapid activation of Rho-kinase during secretion leads to a further increase in F-actin content as compared to shape change. (uni-muenchen.de)
  • Furthermore, the results clearly showed that cofilin dephosphorylation is also independent and upstream of secretion, since the onset of cofilin dephosphorylation was as rapid as secretion in thrombin-stimulated platelets and also occurred in the absence of dense granule secretion in LPA (10 µM)-stimulated platelets. (uni-muenchen.de)
  • It was also found that LGP exhibited marked inhibitory effects on the activation of αIIbβ3 integrin, the secretion of serotonin from granules, and the synthesis of thromboxane A2. (spandidos-publications.com)
  • Final results: Secretion kinetic and dose-response assays showed that platelets from -synuclein-/- mice have defective release from your dense granules and significantly less so from lysosomal granules (Figure 1). (cathepsin-s.com)
  • To understand the mechanism of this defect, we asked irrespective of whether -synuclein is acting as a VAMP-chaperone in platelets and hence modulates secretion by controlling V-SNARE ranges. (cathepsin-s.com)
  • Effects: Secretion kinetic and dose-response assays showed that platelets from -synuclein-/- mice have defective release through the dense granules and significantly less so from lysosomal granules (Figure one). (axlinhibitor.com)
  • Nonetheless, when cells rely on anaerobic glycolysis, like cancer cells and certain innate immune cells upon activation, other metabolic pathways sustain succinate levels, including glutamine-dependent anerplerosis to α-ketoglutarate, and eventually citrate by reductive carboxylation. (haematologica.org)
  • 6 3 In fact, one of the first pieces of evidence for a role of succinate in cancer development was provided by the discovery of pseudohypoxia, which refers to activation of hypoxia signaling pathways under normal oxygen levels. (haematologica.org)
  • Mechanistically, we revealed that nintedanib reduces the TGF-β1-induced phosphorylation of Smad2/3, p38MAPK, and ERK1/2, suggesting that nintedanib acts through both classic and nonclassic signaling pathways of TGF-β1 to prevent HTF activation. (molvis.org)
  • In this review, we discuss the dualistic effects of histamine: how histamine affects inflammation of the immune system through the activation of intracellular pathways that induce the production of inflammatory mediators and cytokines in different immune cells and how histamine exerts regulatory functions in innate and adaptive immune responses. (hindawi.com)
  • Fibrinogen binds to the glycoprotein IIb/IIIa complexes of adjacent platelets, connecting them into aggregates. (msdmanuals.com)
  • Platelet effects result from activation of intracellular adenylate cyclase and from increased cyclic adenosine monophosphate (cAMP) concentrations within platelets. (medscape.com)
  • Epoprostenol potently desensitizes platelets during exposure to heparin by inhibiting platelet activation and by increasing intracellular concentrations of platelet cyclic adenosine monophosphate. (blogspot.com)
  • Several of these models make use of a continuum approach where platelets, platelet agonists, and coagulation factors are treated as chemical species that obey the convection-diffusion-reaction equation for species transport [ 11 - 15 ]. (frontiersin.org)
  • This model falls under the class of hybrid multiscale models where blood velocity and platelet agonists are treated as continuum fields while platelets are resolved explicitly [ 2 - 10 ]. (frontiersin.org)
  • Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca(2+) release from intracellular stores. (nih.gov)
  • Our study presents compelling evidence in support of non-canonical juxtacrine Notch signaling within platelet aggregates that synergizes with physiological agonists to generate occlusive intramural thrombi. (elifesciences.org)
  • Western blotting was used to HDAC5 Inhibitor site assess the levels of the platelet secretory machinery. (cathepsin-s.com)
  • The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. (nature.com)
  • Cells were exposed to one of three chemotactic stimuli: platelet-activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (FMLP), or leukotriene B4 (LTB4). (nih.gov)
  • The physiological agonist thrombin and the pathophysiological relevant agonist lysophosphatidic acid (LPA), which is the main platelet-activating lipid in atherosclerotic plaque, were used as platelet stimuli to address these questions. (uni-muenchen.de)
  • Various stimuli increase cellular levels of SPP by activation of sphingosine kinase (SPHK), the enzyme that catalyzes the phosphorylation of sphingosine. (novusbio.com)
  • In macrophages, HS in combination with inflammatory stimuli leads to enhanced pro-inflammatory activation and increased antimicrobial capacity ( 8 , 12 , 13 , 24 , 25 ), while limiting their regulatory features ( 26 - 29 ). (frontiersin.org)
  • This triggers potent inside out signals inducing ADP release from dense bodies ( Shape change & agonist release ) as well as activating platelet major integrin α IIb β 3 . (biomedcentral.com)
  • Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase. (nih.gov)
  • Our study shows that LIMK-1 activation was mainly Rho-kinase dependent in LPA- and thrombin-stimulated platelets. (uni-muenchen.de)
  • Surprisingly, the activation of LIMK-1 failed to increase cofilin phosphorylation during shape change induced by LPA as well as by thrombin. (uni-muenchen.de)
  • The propagation phase feeds back to amplify the process and prospects to thrombin generation culminating in platelet and fibrin thrombi. (immune-source.com)
  • Of note, in a developing thrombus further activation converts platelets from a proaggregatory to a to pro-coagulant phenotype which enables the assembly of the coagulation reaction complexes (the Tenase and Prothrombinase complex) on the cell surface, necessary for thrombin and fibrin generation. (biomedcentral.com)
  • Thrombin converts fibrinogen into fibrin monomers, and the fibrin monomers polymerize into fibrin polymers that bind aggregated platelets into platelet-fibrin hemostatic plugs. (msdmanuals.com)
  • Coagulation factors interact on platelet and endothelial cell surfaces to produce thrombin , which converts fibrinogen to fibrin. (msdmanuals.com)
  • Thus, Notch pathway can be a potential anti-platelet/anti-thrombotic therapeutic target. (elifesciences.org)
  • Advances in the discovery of novel anti-platelet therapeutics remains an unmet need. (elifesciences.org)
  • This prevention of platelet-graft interaction may be accomplished by administration of established anti-platelet drugs to the brain-dead donor. (rotrf.org)
  • Current pathophysiology studies are focused on the origin of the antibody response, the nature of the antigenic complex and pathologic epitopes, the mechanisms of interindividual differences in platelet activation, and the functions of monocytes and endothelial cells. (immune-source.com)
  • Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. (nature.com)
  • In spite of this, current antithrombotic approaches still fail to prevent thrombotic coronary events in a substantial number of patients 5 , indicating that the complex mechanisms modulating platelet response during activation are not completely understood. (nature.com)
  • Thrombocytopenia is a common feature of hemorrhagic fevers and vascular permeability disorders ( 8 ), but the decrease in platelet counts in acute LF is not low enough to cause spontaneous hemorrhage. (cdc.gov)
  • In turn, the structure and size of platelet aggregates affect blood flow as well as the release and transport of various biochemical species that couple back to platelet activation. (frontiersin.org)
  • Under these conditions, platelets adhere to the damaged intima and form aggregates. (msdmanuals.com)
  • Platelet-leukocyte interaction could have physiopathological relevance and constitutes a new model for studying old and new platelet inhibitory drugs. (nih.gov)
  • The role of platelets will be assessed by administration of various platelet-inhibitory drugs to the brain-dead animal. (rotrf.org)
  • Therefore, we further investigated the inhibitory roles of sesamol in NF-B-mediated platelet function. (tmu.edu.tw)
  • Platelets typically circulate in the bloodstream for 7-10 days and their principal function is to survey the inner lining of blood vessels to detect and seal any breaches in the vasculature by the creation of thrombi. (biomedcentral.com)
  • Like Rho-kinase activation, it was also found that LIMK-1 activation was independent and upstream of integrin IIbβ3 activation. (uni-muenchen.de)
  • The biodirectional nature of integrin mediated signaling allows both extra- and intracellular cues to regulate activation [ 4 ] (Fig. 1 ). (thno.org)
  • Intracellular signaling events that converge on the cytoplasmic domain of integrin tails are also capable of activating the high affinity state. (thno.org)
  • Intracellular signals that result in integrin activation are referred to as 'inside-out' signaling events. (thno.org)
  • Integrin ligation via cell-to-cell and cell-to-matrix contacts transduces intracellular signaling events in a process called 'outside-in' signaling (Fig. 2 ). (thno.org)
  • Platelet integrin α IIb β 3 can also be modulated with a calpain-dependent proteolytic cleavage. (biomedcentral.com)
  • Transcripts/peptides of Notch1 and Delta-like ligand (DLL)-4 were detected in platelets isolated from human blood by RT-qPCR, Western analysis and flow cytometry. (elifesciences.org)
  • However, it is unclear how a single YXXL motif can interact efficiently with Syk, which usually recognizes two tandem YXXL repeats presented as an immunoreceptor tyrosine-based activation motif (ITAM). (ox.ac.uk)
  • Thrombocytopenia and platelet dysfunction contribute to hemorrhagic complications observed in MDS. (ashpublications.org)
  • The impaired homeostasis and platelet dysfunction implicate alterations in the protein C pathway, which might contribute to the loss of endothelial barrier function in fatal infections. (cdc.gov)
  • Conclusions: This research suggests that targeting MZB cells may very well be a fresh therapeutic approach to reduce platelet alloimmunization and reduce the related refractory state. (cathepsin-s.com)
  • Conclusions: This review suggests that targeting MZB cells could possibly be a fresh therapeutic method to minimize platelet alloimmunization and protect against the associated refractory state. (axlinhibitor.com)
  • Many of the features of apoptosis such as membrane fragmentation, microvesiculation and phosphatidylserine (PS) exposure are observed during platelet activation to a procoagulant state, raising the possibility that apoptosis may regulate platelet function. (ashpublications.org)
  • Different dynamics and dose-dependence of procoagulant platelet formation in healthy donors was associated with individual variations in PAR1 and PAR4 activities and particularly by the Ala120Thr polymorphism in the F2RL3 gene encoding PAR4. (ipmnet.ru)
  • Procedures: We examined the phenotype of platelets from synuclein-/- mice. (cathepsin-s.com)
  • Platelet-activating factor-mediated transmembrane signaling in human B lymphocytes is regulated through a pertussis- and cholera toxin-sensitive pathway. (jci.org)
  • Although platelets are anucleated cells, they also express the transcription factor, NF-B, that may exert non-genomic functions in platelet activation. (tmu.edu.tw)
  • Competitive inhibitors of SPHK block formation of SPP and selectively inhibit cellular proliferation induced by a variety of factors, including platelet-derived growth factor (e.g. (novusbio.com)
  • The potential role of platelet-activating factor (PAF)-acether and of IL-5 as an eosinophil-proliferating, activating, and/or recruiting mediator in asthma led us to study the effects of human (h) rIL-5 (hrIL-5) and PAF-acether, alone or combined, on isolated guinea pig eosinophils. (pasteur.fr)
  • Receptores específicos en las membranas celulares que reaccionan con el FACTOR DE CRECIMIENTO DERIVADO DE PLAQUETAS, sus análogos o antagonistas. (bvsalud.org)
  • Because the human Na + -H + antiporter (NHE-1) possesses a C-terminal consensus sequence for carboxyl methylation, we examined the role of protein carboxyl methylation in the regulation of intracellular pH homeostasis. (elsevierpure.com)
  • Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. (nih.gov)
  • Intensive glucose control with insulin in patients with an acute coronary syndrome reduces platelet reactivity during hospitalization, compared to conventional control. (revespcardiol.org)
  • However, the effect of strict, long-term glucose control on platelet reactivity in these patients remains uncertain. (revespcardiol.org)
  • 180 mg/dL), on platelet reactivity after hospital discharge in patients with an acute coronary syndrome and hyperglycemia. (revespcardiol.org)
  • Progress in therapy is usually hampered by the difficulties of inadequate positive predictive value of antibody detection and clinical scores in suspected HIT, very limited availability of practical platelet activation assays, and the paucity of new agents in human clinical trials. (immune-source.com)
  • HIT therapy needs improvement that could come from better diagnostics in the form of practical platelet activation assays, and from combos of rational therapeutics targeting past due and early guidelines in pathophysiology. (immune-source.com)
  • Addition of platelets at different times after leukocyte activation resulted in progressively reduced cytoplasmic Ca2+ increase. (nih.gov)
  • Compared with the normal diet group, the diabetic group had significantly increased plasma EMP-PDI content and accelerated platelet activation by increased GP IIb/IIIa expression. (aging-us.com)
  • Significantly, PF4As inhibited ULC formation at all PF4 : Hep ratios tested, and both antagonists prevented cellular activation by ULC and HIT antibodies. (immune-source.com)
  • Interestingly, it has been shown that platelets contain a broad spectrum of RNA molecules, including, in addition to mRNAs and miRNAs, also pre-mRNAs and a role of mRNA splicing in regulation of platelet protein synthesis has been proposed 18 , 19 . (nature.com)
  • The morphological and functional changes of platelets require a drastic remodeling of the actin cytoskeleton regulated by numerous actin-binding proteins and signaling molecules such as the family of Rho-GTPases. (uni-muenchen.de)
  • Further, the toxins did not appear to act through elevation of intracellular levels of cAMP. (jci.org)
  • It then highlights the crucial role of ectodomain shedding and microvesiculation in the propagation of "platelet storage lesion" which may affect the post-transfusion efficacy of platelet components. (biomedcentral.com)
  • Synuclein seems to be the sole member from the synuclein household existing in platelets and it is quite abundant. (cathepsin-s.com)
  • Aims: To deal with the purpose of -synuclein in platelet exocytosis. (cathepsin-s.com)
  • Synuclein seems to be the sole member with the synuclein family members existing in platelets and is quite IL-1 Antagonist Storage & Stability abundant. (axlinhibitor.com)
  • Aims: To tackle the role of -synuclein in platelet exocytosis. (axlinhibitor.com)
  • Supplemental western blotting experiments demonstrated the presence from the -synuclein-interactor Cysteine String Protein, extra a whole new element to the acknowledged platelet secretory machinery (Figure 2). (axlinhibitor.com)