Abstract:
:Hyperglycaemia impairs fibrinolytic activity on the surface of endothelial cells, but the underlying mechanisms are not fully understood. In this study, we tested the hypothesis that hyperglycaemia causes dysfunction of the endothelial membrane protein annexin A2, thereby leading to an overall reduction of fibrinolytic activity. Hyperglycaemia for 7 days significantly reduced cell surface fibrinolytic activity in human brain microvascular endothelial cells (HBMEC). Hyperglycaemia also decreased tissue type plasminogen activator (t-PA), plasminogen, and annexin A2 mRNA and protein expression, while increasing plasminogen activator inhibitor-1 (PAI-1). No changes in p11 mRNA or protein expression were detected. Hyperglycaemia significantly increased AGE-modified forms of total cellular and membrane annexin A2. The hyperglycemia-associated reduction in fibrinolytic activity was fully restored upon incubation with recombinant annexin A2 (rA2), but not AGE-modified annexin A2 or exogenous t-PA. Hyperglycaemia decreased t-PA, upregulated PAI-1 and induced AGE-related disruption of annexin A2 function, all of which contributed to the overall reduction in endothelial cell surface fibrinolytic activity. Further investigations to elucidate the underlying molecular mechanisms and pathophysiological implications of A2 derivatisation might ultimately lead to a better understanding of mechanisms of impaired vascular fibrinolysis, and to development of new interventional strategies for the thrombotic vascular complications in diabetes.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Dai H,Yu Z,Fan X,Liu N,Yan M,Chen Z,Lo EH,Hajjar KA,Wang Xdoi
10.1160/TH12-12-0944subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1070-8issue
6eissn
0340-6245issn
2567-689Xpii
12-12-0944journal_volume
109pub_type
杂志文章abstract::Von Willebrand factor (vWF) plays an essential role in platelet adhesion and thrombus formation. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 antigen levels compared to controls. Little is known about vWF and ADAMTS13 in AF patients treated with cardioversion (CV). Thus we invest...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-09-0615
更新日期:2011-03-01 00:00:00
abstract::The first step of coagulation factor XIII (FXIII) activation involves cleavage of the FXIII activation peptide (FXIII-AP) by thrombin. However, it is not known whether the FXIII-AP is released into plasma upon cleavage or remains attached to activated FXIII. The aim of the present work was to study the structure of fr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-06-01 00:00:00
abstract::An association has been reported between thrombotic events and the use of L-asparaginase (ASP) in children with acute lymphoblastic leukaemia (ALL). The mechanism for thrombosis is likely related to an acquired antithrombin deficiency. Since a primary prophylaxis using antithrombin concentrates may prevent thrombosis,...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1160/TH02-11-0283
更新日期:2003-08-01 00:00:00
abstract::The interaction of beta 2-glycoprotein-I (beta 2-G-I), a plasma constituent of unknown function, with blood platelets was studied. The following results were obtained: 1) beta 2-G-I binds to washed human platelets isolated by centrifugation (WP) at one kind of specific, saturable binding sites. The dissociation consta...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-08-30 00:00:00
abstract::Hyperhomocysteinemia is a risk factor of venous thromboembolism. The risk of recurrence in patients with hyperhomocysteinemia is unknown, and the optimal therapy for these patients after acute venous thromboembolism is uncertain. In a multicenter study, 264 patients with an objectively documented single episode of idi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::It is known that the fibrinolysis inhibitors in the human placenta are proteins which, in vitro, block urokinase plasminogen activation and are for this reason called urokinase inhibitors. In the present study it was found, for the first time, that a slow-molecular urokinase inhibitor also occurs in the human placenta...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1980-02-29 00:00:00
abstract::The role of circulating microparticles (MP) of different origin and tissue factor (TF)-bearing in overweight and obese patients with and without metabolic syndrome is still a matter of debate. In a case-control study, the presence of hypercoagulability was evaluated in overweight and obese patients by measuring MP, th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-02-0156
更新日期:2015-01-01 00:00:00
abstract::Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim w...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-12-0946
更新日期:2017-10-01 00:00:00
abstract::Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numb...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH17-06-0433
更新日期:2017-12-01 00:00:00
abstract::Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on plasma factor/inhibitor composition. Plasma factor (F) compositions (II, V, VII, VIII, IX, X), ant...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-02-0091
更新日期:2010-08-01 00:00:00
abstract::Assembly of fibronectin into the provisional fibrillar matrix of embryonic tissues and wounds is a complicated process by which the intracellular cytoskeleton determines the pattern of assembly of extracellular matrix and vice versa. Assembly is restricted to dimeric fibronectin molecules with intact N-terminal module...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1995-07-01 00:00:00
abstract::An increased prevalence of hypertension is reported in haemophilia patients, but data from large, unbiased studies are lacking. The aim of our study was to cross-sectionally assess the prevalence of hypertension in a large cohort of 701 haemophilia patients. Blood pressure (BP) measurements performed in 386 Dutch and ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH12-05-0313
更新日期:2012-10-01 00:00:00
abstract::Expression of isolated beta integrin cytoplasmic domains in cultured endothelial cells was reported to induce cell detachment and death. To test whether cell death was the cause or the consequence of cell detachment, we expressed isolated integrin beta1 cytoplasmic and transmembrane domains (CH1) in cultured human umb...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2005-11-01 00:00:00
abstract::Type I von Willebrand disease (vWD) Vicenza is a rare variant with autosomal dominant transmission, characterized by the presence of supranormal von Willebrand factor (vWF) multimers in plasma, similar to those normally found in endothelial cells and megakaryocytes. The patients have very low levels of plasma vWF cont...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Unstimulated human platelets from normal volunteers adhere to sulfatides (galactosylceramide-I3-sulfate) as single cells but do not adhere appreciably to other lipids including gangliosides, neutral glycolipids, phospholipids or cholesterol-3-SO4. Platelet adhesion to sulfatide is saturable and dose-dependent, reaches...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-05-06 00:00:00
abstract::Human endothelial cells isolated from umbilical cords were solubilized in Triton X-100 and examined by crossed immunoelectrophoresis using rabbit antiserum against endothelial cells. Endogenous labelling of the endothelial cell proteins with 14C-mannose followed by crossed immunoelectrophoresis and autoradiography rev...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-04-12 00:00:00
abstract::The effects of human activated protein C (APC) and thrombin on plasminogen activator inhibitor (PAI-1) released from cultured human umbilical endothelial cells, grown in serum-free 35S-methionine containing medium, were studied in two ways: measurement of PAI-1 activity with an amidolytic assay, and immunoprecipitatio...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-04-07 00:00:00
abstract::In order to explore the mechanisms leading to conformational changes of the vitronectin receptor alphavbeta3 following ligand or divalent cation binding, we have investigated the expression of epitopes known as ligand-induced binding sites (LIBS) on beta3 cytoplasmic tail mutants expressed in CHO cells. Truncation of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::Multifunctional proteins, e.g. high molecular weight kininogen (HK, 120 kDa) and the homotrimer, thrombospondin (TSP, 540 kDa), which have more than one domain on a single polypeptide chain, are particularly well-suited to be structural elements of extracellular matrices because of their ability to bind to several mac...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::A method is described for the purification of antiactivator from bovine euglobulin-free serum by means of gelfiltration and ion exchange chromatography. The purified antiactivator has no antifibrinolytic activity. It has a molecular weight of about 115,000 and it appears to be a gamma globulin. The dissociation consta...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-10-31 00:00:00
abstract::Microvascular thrombosis is considered an important pathogenetic factor in renal failure associated with obstructive jaundice but the mechanisms leading to fibrin deposition are still unknown. The plasma levels of plasminogen activator inhibitor (PAI) in 29 patients with obstructive jaundice were found significantly i...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-08-30 00:00:00
abstract::When compared to normal megakaryocytes, those from a patient with the giant platelet syndrome exhibited numerous cytochemical abnormalities. These reflected disturbances in the metabolism of RNA, glycogen, arginine-rich histone, and various glycolytic enzymes. Ultrastructural studies of the abnormal megakaryocytes als...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1977-10-31 00:00:00
abstract::Homocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH05-05-0313
更新日期:2005-11-01 00:00:00
abstract::The antithrombotic efficacies of the coagulation factor Xa inhibitor recombinant tick anticoagulant peptide (rTAP) and heparin were compared in a canine model of left circumflex (LCX) coronary artery electrolytic lesion. Intravenous infusions of saline (controls), rTAP (50 micrograms/kg/min continuous infusion) or hep...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Current thrombolytic strategies have a number of important shortcomings including resistance to recanalization and development of acute reocclusion. The purpose of this study was to investigate whether the lysis of venous thrombi by streptokinase could be enhanced by SR 46349, a novel 5-HT2 receptor antagonist, or clo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) is one of the main regulators of the tissue factor (TF) pathway of coagulation. To tether human TFPI to the cell surface, full length or truncated TFPI lacking the third Kunitz domain were fused with domains three and four and the carboxy-terminal sequence of human CD4. Construct...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND: Clinical effectiveness of recombinant human soluble thrombomodulin (rhTM) in sepsis or sepsis-induced coagulopathy remains a matter of dispute. Recently, the Sepsis Coagulopathy Asahi Recombinant LEThrombomodulin (SCARLET) trial, the latest multinational multi-centre phase III randomized controlled trial, w...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析
doi:10.1055/s-0038-1676345
更新日期:2019-01-01 00:00:00
abstract::Among the nine ellagitannins, rugosin E was the most potent platelet aggregating agent with an EC50 of 1.5 +/- 0.1 microM in rabbit platelets and 3.2 +/- 0.1 microM in human platelets. The aggregations caused by rugosin E and ADP were inhibited by EGTA, PGE1, mepacrine, sodium nitroprusside and neomycin, but not by in...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Graduated elastic compression stockings (GECS) are commonly used in the primary prevention of deep vein thrombosis (DVT); however, their role in preventing recurrent DVT and also post-thrombotic syndrome is less well established. The aim of this review was to investigate the effect of GECS after DVT. A literature sear...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2006-10-01 00:00:00
abstract::Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. We have shown previously that PAI-1 biosynthesis in cultured cells depends on several factors in serum. Because platelets are richly endowed with specific growth factors and because the release reaction is an integral...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00