Abstract：
:Several studies have highlighted a specific role for membrane cholesterol domains in platelet signalling. Upon adhesion to von Willebrand factor (VWF) or collagen, cholesterol-rich domains (CRDs) accumulate in filopodial extensions and selectively harbour counterpart receptors (GPIb and GPVI) and associated signalling molecules. In the present study we have addressed the role of membrane cholesterol in Ca(2+) signalling and secretion during the interaction of platelets with VWF and collagen. VWF/ristocetin-induced platelet aggregation was delayed after treatment with methyl beta-cyclodextrin (mbCD), but the maximal aggregation response was not affected. Platelet spreading but not adhesion to immobilised VWF under flow was attenuated by cholesterol removal, and accompanied by moderate lowering in the spiking Ca(2+) response. On the other hand, platelet interaction with collagen was quite sensitive to cholesterol depletion. Platelet aggregation decreased after treatment with mbCD, and Ca(2+) responses were decreased, both under static and flow conditions. Cholesterol depletion affected the secondary feedback activation via release of thromboxane A(2) and ADP. The collagen-induced secretion of alpha granules and surface translocation of P-selectin and CD63 was also critically affected by cholesterol depletion. Confocal microscopy showed localization of p-Tyr at sites of contact with substrate and other platelets, where also CRDs accumulate. Our data thus reveal a more critical role for membrane cholesterol in collagen-induced than in VWF-induced Ca(2+) signalling, and furthermore support the concept that secondary activation responses are dependent on intact CRDs.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
van Lier M,Verhoef S,Cauwenberghs S,Heemskerk JW,Akkerman JW,Heijnen HFdoi
10.1160/TH07-08-0528subject
Has Abstractpub_date
2008-06-01 00:00:00pages
1068-78issue
6eissn
0340-6245issn
2567-689Xpii
08061068journal_volume
99pub_type
杂志文章abstract：:Incubation of platelet-rich plasma (PRP) with ouabain, an inhibitor of sodium/potassium ATPase (Na+/K+ ATPase), induced a significant rise in basal platelet intracellular calcium concentration [( Ca2+]i) when measured using fura 2. Ouabain induced an enhanced aggregation response to low doses of collagen in both PRP a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-11-24 00:00:00
abstract：:We developed an ELISA test to measure the binding of plasma von Willebrand factor (vWF) to arterial microfibrils and compared this interaction to the binding of vWF to collagen under the same conditions. We found that vWF binds to microfibrils in a similar manner as it binds to collagen: the binding was independent of...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-08-13 00:00:00
abstract：:Carboxypeptidase U (CPU, CPB2, TAFIa) is a basic carboxypeptidase that is able to attenuate fibrinolysis. The inactive precursor procarboxypeptidase U is converted to its active form by thrombin, the thrombin-thrombomodulin complex or plasmin. The aim of this study was to investigate and characterise the time course o...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-02-0097
更新日期：2017-07-26 00:00:00
abstract：:Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and is considered as an attractive drug target. We generated two different antibody fragments, an antigen-binding fragment (Fab) and a single-chain variable fragment (scFv), derived from three distinct monoclonal antibodies (MAs) that inhibit t...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH08-09-0834
更新日期：2009-07-01 00:00:00
abstract：:As an adjunct to a European multicentre prospective study, five quality assessment (QA) exercises, spanning a period of 2.5 years, were undertaken. In these, fifteen laboratories from eight countries each performed ten haemostatic factor assays. The design of the QA exercises allowed the between-duplicate, between-day...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：1991-02-12 00:00:00
abstract：:In The Netherlands, a particular coagulometer method for prothrombin time (PT) determination with reduced sample and reagent volumes is used by 62% of the laboratories controlling oral anticoagulant therapy. This "micro-method" has been calibrated against the manual tilt-tube technique for PT determination by six Dutc...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,多中心研究
doi：
更新日期：1989-04-25 00:00:00
abstract：:A series of aromatic amidino compounds were investigated for their inhibitory effect on platelet agglutination and platelet aggregation. Agglutination of fresh or fixed platelets was produced by bovine plasma or by human plasma in combination with ristocetin, while aggregation of fresh platelets was induced by ADP, th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-04-30 00:00:00
abstract：:Inhibition of adenylate cyclase in intact platelets by addition of compounds such as 2', 5' - dideoxyadenosine prevented the inhibition of platelet aggregation by PGE1 but did not affect the responses of platelets to aggregating agents in the absence of PGE1. This confirms that cyclic AMP mediates the effects of PGE1 ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1978-10-31 00:00:00
abstract：:Thrombin triggers activation of platelets through protease-activated receptor 1 (PAR-1) and PAR-4. Both receptors are widely expressed and exert multiple platelet-independent functions. PAR signalling contributes to healing responses after injury, by promoting cytokine activity and cellular growth and mobility. Uncont...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH17-03-0219
更新日期：2017-11-01 00:00:00
abstract：:Idarucizumab, a Fab fragment directed against dabigatran, produced rapid and complete reversal of the anticoagulation effect of dabigatran in animals and in healthy volunteers. The Study of the REVERSal Effects of Idarucizumab in Patients on Active Dabigatran (RE-VERSE AD™) is a global phase 3 prospective cohort study...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH15-03-0192
更新日期：2015-07-01 00:00:00
abstract：:In hereditary angioedema (HAE), normal C1-inhibitor (C1-INH) is low and the contact system activated. Recently, the findings of a tissue factor mutant selectively deficient in promoting the conversion of FVII to FVIIa, but with retained cofactor for FVIIa, made it possible to examine reliably the pre-existing content ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. How...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:Fibrinogen Matsumoto V (M-V) is a dysfibrinogen identified in a 52-year-old woman with systemic lupus erythematous. The triplet AGG encoding the amino acid residue Aalpha19 was replaced by GGG, resulting in the substitution of Arg-->Gly. Residue Aalpha19 has been shown to be one of the most important amino acids in th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Nipah virus (NiV) is a highly pathogenic paramyxovirus that was first isolated in 1999 during an outbreak in Malaysia. In contrast to other paramyxoviruses NiV infects many mammalian species. Because of its zoonotic potential, the high pathogenicity and the lack of therapeutic treatment, NiV was classified as a biosaf...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-05-0310
更新日期：2009-12-01 00:00:00
abstract：:Wide variations in procoagulant properties, lipid composition and ultrastructure of five commonly used APTT methods have been demonstrated. Performance of the methods with a range of coagulation abnormalities has been ranked. Most of the reagents obtained a high score with one or more defects, but a low score with oth...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-04-30 00:00:00
abstract：:Duplex ultrasound is the first-line diagnostic test for detecting lower limb deep-vein thrombosis (DVT) but it is time consuming, requires patient transport, and cannot be interpreted by most physicians. The accuracy of emergency physician-performed ultrasound (EPPU) for the diagnosis of DVT, when performed at the bed...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,meta分析,评审
doi：10.1160/TH12-07-0473
更新日期：2013-01-01 00:00:00
abstract：:Platelet aggregation and adenine nucleotides in platelets have been studied in thirteen patients with myeloproliferative disorders. ADP induced aggregation was abnormal in two patients, but collagen induced aggregation was impaired in 11 patients. The concentrations of ATP and ADP in resting platelets in the patients ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1979-06-30 00:00:00
abstract：:A pulmonary embolism model in hamsters was used for the quantitative evaluation of the thrombolytic and pharmacokinetic properties of variants of tissue-type plasminogen activator (t-PA). A 25 microliters 125I-fibrin labeled human plasma clot was made in vitro and injected into the jugular vein of heparinized hamsters...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-02-12 00:00:00
abstract：:We investigated the extent to which fibroblasts isolated from diverse tissues differ in their capacity to modulate inflammation by comparing the global gene expression profiles of cultured human fibroblasts from skin, acute and chronically inflamed synovium, lymph node and tonsil. The responses of these fibroblasts to...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-04-0208
更新日期：2003-10-01 00:00:00
abstract：:Heparanase is implicated in angiogenesis and tumour progression. We previously demonstrated that heparanase might also affect the haemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (TF). Peptides that we generated from TF pathway ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-02-0119
更新日期：2016-09-27 00:00:00
abstract：:Pregnancy and delivery have measurable effects on haemostatic and immunological changes. Degradation of fibrinogen induces significant structural and conformational modulation and leads to the progressive loss of antigenic sites present on the parent molecule but also exposes some new sites. These neoantigens may be r...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:We report on three unrelated individuals with the same uncommon type of dysfibrinogenemia, originating from Bergamo, Essen and Perugia. None of them showed bleeding symptoms while the Bergamo patient and members of her family presented with a thrombotic tendency. The presence of a defective fibrinogen was suggested by...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-12-15 00:00:00
abstract：:Interactions between the uPA receptor (uPAR) and various integrins, including alpha(5)beta(1), are known to modulate integrin-dependent cell adhesion, and we have shown that the integrin-associated tetraspanin protein CD82 down-regulates uPAR-dependent plasminogen activation by affecting alpha(5)beta(1) cellular local...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2009-05-01 00:00:00
abstract：:The effect of supernatant from phorbol myristate acetate (PMA) stimulated human polymorphonuclear granulocytes (PMN) on human factor VII was studied in vitro. The supernatant caused a rapid loss in factor VII coagulant activity by the action of human leukocyte elastase (HLE) and cathepsin G in the supernatant, as demo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:Severe type I plasminogen deficiency is the underlying cause of ligneous conjunctivitis, a rare disease characterized by wood-like pseudomembranes developing on the ocular and extraocular mucosa. Two unrelated female patients with ligneous conjunctivitis and moderate hypoplasminogenemia are described. Being of fertile...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-07-01 00:00:00
abstract：:Prolonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinica...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-07-0481
更新日期：2004-03-01 00:00:00
abstract：BACKGROUND: Accurate diagnosis of symptomatic low von Willebrand factor (VWF) remains a major challenge in von Willebrand disease (VWD). However, present tests do not adequately take into account flow forces that, at very high shear rates, reveal a weakness in the VWF-platelet glycoprotein glycoprotein Ib bond in norma...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1709525
更新日期：2020-05-01 00:00:00
abstract：:The object was to assess the variability in displayed International Normalised Ratio (INR) between monitors of the same manufacture using whole blood samples from the same subjects. Two brands of monitor, CoaguChek Mini and the TAS PT-NC were tested. 14 instruments of each brand were tested on the same day at the same...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-12-01 00:00:00
abstract：:Hyperglycemia-induced mitochondrial overproduction of reactive oxygen species leads to the activation of different biochemical pathways involved in endothelial damage of the diabetic retina. Tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone] is a dicarbonyl scavenger in the millimolar range and a transition metal ion che...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2006-04-01 00:00:00
abstract：:The mechanism of thrombin induction of tissue- and urokinase-type plasminogen activator (t-PA and u-PA) biosynthesis was investigated in cultured human fetal lung fibroblast cells, IMR-90. Northern blot analysis of total RNA from thrombin-treated cells showed marked accumulations of both t-PA and u-PA mRNA during 24 h...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
