• Fibrinogen molecules then interconnect the platelets, serving as the basis for platelet aggregation. (wikipedia.org)
  • This complex interacts with fibrinogen and thus plays an important role in platelet aggregation and adhesion to endothelial surfaces. (wikipedia.org)
  • Activation of this complex initiates the platelet aggregation and the formation of primary platelet plug, a fibrin clot. (wikipedia.org)
  • The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence. (hemostasis.com)
  • Aspirin, glycoprotein (GP) IIb/IIIa inhibitors, and clopidogrel have an inhibitory effect on platelet activation and aggregation. (medscape.com)
  • 1. Khaspekova SG, Ziuriaev IT, Iakushkin VV, Golubeva NV, Ruda MIa, Mazurov AV. (2011) [Platelet aggregation upon acetylsalicylic acid and clopidogrel treatment and glycoprotein IIb/IIIa content in patients with acute coronary syndrome]. (yoproteins.eu)
  • 3. Sirotkina OV, Khaspekova SG, Zabotina AM, Shimanova YV, Mazurov AV. (2007) Effects of platelet glycoprotein IIb-IIIa number and glycoprotein IIIa Leu33Pro polymorphism on platelet aggregation and sensitivity to glycoprotein IIb-IIIa antagonists. (yoproteins.eu)
  • 4. Naimushin YA, Mazurov AV. (2004) Von Willebrand factor can support platelet aggregation via interaction with activated GPIIb-IIIa and GPIb. (yoproteins.eu)
  • 2001) [Inhibition of thrombocyte aggregation by F(ab')2-fragments of monoclonal antibodies FraMon (CRC64) to glycoproteins IIb-IIIa]. (yoproteins.eu)
  • 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 mouse monoclonal antibody PAC-1 recognizes an extracellular activation-induced conformational epitope PAC-1 on CD41/CD61 complex (gpIIb/IIIa), also known as integrin alpha IIb beta 3, a receptor which mediates platelet aggregation. (exbio.cz)
  • Upon blood vessel damage, this receptor binds to a variety of proteins including von Willebrand factor, fibrinogen, fibronectin and vitronectin, and it is involved in platelet aggregation. (exbio.cz)
  • 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)
  • Bitiscetin has recently been shown to induce von Willebrand factor (vWF)-dependent aggregation of fixed platelets (Hamako J, et al, Biochem Biophys Res Commun 226:273, 1996). (ashpublications.org)
  • 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)
  • Membrane glycoproteins GPIa/IIa, GPVI and probably GPIV as well, function as collagen receptors, engaged in platelet adhesion to collagen. (wikipedia.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)
  • This process relies on the destruction of disulfide bonds present on these receptors, such as Cys5-Cys435, Cys663-Cys687, and a third Cys-rich repetitive zone, to be transformed into the ligand-binding, high-affinity state and evoke conformational changes in GP IIb/IIIa receptors [ 10 ]. (aging-us.com)
  • In this mechanism, vWF acts as a molecular bridge between constituents of the subendothelium, like collagen, and receptors of the platelet membrane, primarily the GPIb. (ashpublications.org)
  • 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)
  • Glycoprotein IIb/IIIa (GPIIb/IIIa, also known as integrin αIIbβ3) is an integrin complex found on platelets. (hemostasis.com)
  • It is an important collagen receptor involved in collagen-induced platelet activation and adhesion. (wikipedia.org)
  • The gpIIb/IIIa receptor is a target of several drugs including abciximab, eptifibatide, tirofiban. (hemostasis.com)
  • 2001) A novel viper venom metalloproteinase, alborhagin, is an agonist at the platelet collagen receptor GPVI. (yoproteins.eu)
  • 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)
  • CD41 (platelet glycoprotein IIb, integrin alpha IIb) is composed of two subunits (120 kDa transmembrane alpha chain and 23 kDa extracellular beta chain) and interacts with CD61 (platelet glycoprotein IIIa, integrin beta 3) in the presence of calcium to form a functional adhesive protein receptor. (exbio.cz)
  • 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)
  • The binding of von Willebrand factor (vWF) results in conformational changes within the GPIb-V-IX complex. (wikipedia.org)
  • V ON WILLEBRAND FACTOR (vWF) is a multimeric glycoprotein (GP) that plays a key role, under high-shear conditions, in the initial attachment of platelets to the extracellular matrix of the endothelial cells after injury of the vessel wall. (ashpublications.org)
  • 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)
  • During thrombus formation, circulating prothrombin is activated to the active clotting factor, thrombin, by activated platelets. (medscape.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)
  • 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)
  • When the blood vessel wall is damaged, platelet membrane glycoproteins interact with the extracellular matrix. (wikipedia.org)
  • The IIb / IIIa complex is a major platelet membrane component. (wikipedia.org)
  • These subunits form Ca2+ - dependent complex on the surface of platelet membrane in a 1:1 ratio. (wikipedia.org)
  • Stimulation of platelet functional reactions and binding with membrane glycoproteins. (yoproteins.eu)
  • 8. Khaspekova SG, Vyzova TV, Lukin VV, Tikhomirov OIu, Berndt M, Kouns W, Mazurov AV. (1996) [Conformational changes of the platelet membrane glycoprotein IIb-IIIa complex stimulated by a monoclonal antibody to the N-terminal segment of glycoprotein IIIa]. (yoproteins.eu)
  • 9. Khaspekova SG, Vlasik TN, Byzova TV, Vinogradov DV, Berndt MC, Mazurov AV. (1993) Detection of an epitope specific for the dissociated form of glycoprotein IIIa of platelet membrane glycoprotein IIb-IIIa complex and its expression on the surface of adherent platelets. (yoproteins.eu)
  • Shattil SJ, Hoxie JA, Cunningham M, Brass LF: Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. (exbio.cz)
  • The antibody is specific to the integrin complex alpha 2b beta 3, but not to the dissociated integrins. (yoproteins.eu)
  • The antibody reacts with human platelets and megakaryocytes. (yoproteins.eu)
  • The antibody does not react with platelets from patients with the hereditary deficiency of GP IIb-IIIa (Glanzmann's thrombasthenia). (yoproteins.eu)
  • Autoimmune anti-HIV-1gp120 antibody with antiidiotype-like activity in sera and immune complexes of HIV-1-related immunologic thrombocytopenia. (jci.org)
  • The binding of vWF to platelets involves glycoprotein (GP) Ib because it was totally blocked by monoclonal antibody (MoAb) 6D1 directed towards the vWF-binding site of GPIb. (ashpublications.org)
  • The αIIb (GPIIb) is composed of two subunits linked by disulfide bridges. (wikipedia.org)
  • At the site of the thrombus, the binding of tPA and plasminogen to the fibrin surface induces a conformational change that facilitates the conversion of plasminogen to plasmin and dissolves the clot. (medscape.com)
  • The surface expression of this complex shows high variability, particularly in relation to the polymorphism of GPIa subunit gene. (wikipedia.org)
  • 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)
  • PEG-precipitable complexes bind to platelets in a saturation-dependent manner. (jci.org)
  • Thus, our data support the hypothesis that an interaction between the A1 and A3 domains exists that may play a role in the function of vWF by regulating the ability of the A1 domain to bind to platelet GPIb. (ashpublications.org)
  • Atherosclerosis starts with dysfunctional changes in the endothelium induced by disturbed shear stress which can lead to endothelial and platelet activation, adhesion of monocytes on the activated endothelium, and differentiation into proinflammatory macrophages, which increase the uptake of oxidized LDL (oxLDL) and turn into foam cells, exacerbating the inflammatory signalling. (hindawi.com)
  • 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)
  • The binding between GPIbα and vWF mediates the capture of platelets to the injured vascular wall. (wikipedia.org)
  • Neither affinity-purified Ab1 nor Ab2 binds to platelets. (jci.org)
  • However, the combination of Ab1 and Ab2 (preincubated for 2 h at 22 degrees C) binds to platelets in a saturation-dependent manner at an optimum ratio range of 10-20:1. (jci.org)
  • In the presence of bitiscetin, vWF binds to platelets in a dose-dependent and saturable manner. (ashpublications.org)
  • Shattil SJ, Cunningham M, Hoxie JA: Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. (exbio.cz)
  • The interaction with collagen leads to stabilization of the platelets. (wikipedia.org)
  • 7. Smirnova IV, Khaspekova SG, Ignatov VV, Mazurov AV. (1998) Interaction of wheat germ agglutinin and concanavalin A with platelets. (yoproteins.eu)
  • Therefore, with the aim to summarize the current knowledge on the initiation of the atherosclerotic process, in this paper, we review the early markers of atherosclerosis and we address the main therapeutic targets for preventing atheroma formation at its very initial stages focusing on inflammation, oxidative stress, endothelial dysfunction, and the interaction between platelets and endothelium. (hindawi.com)
  • The localization of the binding site of bitiscetin within the A3 domain was further supported by showing that MoAb to vWF, which are specific for this domain and block the interaction between vWF and collagen, are potent inhibitors of the binding of bitiscetin to vWF and consequently of the bitiscetin-induced binding of vWF to platelets. (ashpublications.org)
  • The binding of vWF to the latter can be initiated by high-shear conditions 1 that contribute to a shape change of the vWF molecule and to its interaction with GPIb. (ashpublications.org)
  • Knockin of human VWF exon 28 and crossbreeding with hGPIbα Tg generated a humanized mouse model of platelet GPIbα-VWFA1 interaction. (ashpublications.org)
  • This complex is located mainly on endothelial cells but also on smooth muscle cells, macrophages and platelets. (wikipedia.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)
  • The αIIbβ3 integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34+cord blood cells to megakaryocytes. (wikipedia.org)
  • We have purified bitiscetin from Bitis arietans venom and investigated the mechanism whereby it promotes a form of vWF that is reactive with platelets. (ashpublications.org)
  • Thus, Notch pathway can be a potential anti-platelet/anti-thrombotic therapeutic target. (elifesciences.org)
  • They are designed by either making changes in an existing peptide or by designing similar molecules that functional equivalence to peptides 12 . (ijpsr.com)
  • Existence of functional Notch signaling in enucleate platelets remains elusive. (elifesciences.org)
  • 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)
  • In the resting state the contact between the two protein subunits (necessary for the complex activation) is prevented by aggregin, which disables their contact necessary for the complex activation. (wikipedia.org)
  • The purpose of this study was to investigate the release of Endothelial microparticle (EMP)-associated protein disulfide isomerase (PDI) after endothelial cell injury induced in diabetes and the changes in platelet activation. (aging-us.com)
  • This suggests that the mechanism of platelet activation in the diabetic state has not been fully elucidated. (aging-us.com)
  • Platelet integrin α IIb β 3 can also be modulated with a calpain-dependent proteolytic cleavage. (biomedcentral.com)
  • Notably, herein the changes are time-dependent and not controllable. (biomedcentral.com)
  • Patients completely lack the ability to aggregate platelets. (wikipedia.org)
  • [ 2 ] In 1958, streptokinase was first used in patients with acute myocardial infarction (AMI), and this changed the focus of treatment. (medscape.com)
  • 2010) [Glycoprotein IIb-IIIa antagonist Monafram in primary angioplasty of patients with acute coronary syndrome without st segment elevation]. (yoproteins.eu)
  • We suggest that the anti-HIV-1gp120 antiidiotype-like complex contributes to the markedly elevated platelet Ig and C3 level of HIV-1-ITP patients and propose that this may contribute to their thrombocytopenia. (jci.org)
  • The EMP-PDI content and GP IIb/IIIa expression of mice platelets were determined. (aging-us.com)
  • We demonstrate expression of Notch1, its ligand DLL-4 and their respective transcripts in human platelets. (elifesciences.org)
  • then, their effects on the platelets of normal C57 mice were characterized. (aging-us.com)
  • 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)
  • 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)
  • The leading role in the elimination of high-stress injury is taken by the glycoprotein Ib-IX-V complex. (wikipedia.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)
  • STEMI, transmural MI) is myocardial necrosis with ECG changes showing ST-segment elevation that is not quickly reversed by nitroglycerin or showing new left bundle branch block. (msdmanuals.com)