Abstract：
:Shiga toxin (Stx)-mediated injury to vascular endothelial cells in the kidneys, brain and other organs underlies the pathogenesis of haemolytic uraemic syndrome (HUS) caused by enterohaemorrhagic Escherichia coli (EHEC). We present a direct and comprehensive comparison of cellular injury induced by the two major Stx types, Stx1 and Stx2, in human brain microvascular endothelial cells (HBMECs) and EA.hy 926 macrovascular endothelial cells. Scanning electron microscopy of microcarrier-based cell cultures, digital holographic microscopy of living single cells, and quantitative apoptosis/necrosis assays demonstrate that Stx1 causes both necrosis and apoptosis, whereas Stx2 induces almost exclusively apoptosis in both cell lines. Moreover, microvascular and macrovascular endothelial cells have different susceptibilities to the toxins: EA.hy 926 cells are slightly, but significantly (∼ 10 times) more susceptible to Stx1, whereas HBMECs are strikingly (≥ 1,000 times) more susceptible to Stx2. These findings have implications in the pathogenesis of HUS, and suggest the existence of yet to be delineated Stx type-specific mechanisms of endothelial cell injury beyond inhibition of protein biosynthesis.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Bauwens A,Bielaszewska M,Kemper B,Langehanenberg P,von Bally G,Reichelt R,Mulac D,Humpf HU,Friedrich AW,Kim KS,Karch H,Müthing Jdoi
10.1160/TH10-02-0140subject
Has Abstractpub_date
2011-03-01 00:00:00pages
515-28issue
3eissn
0340-6245issn
2567-689Xpii
10-02-0140journal_volume
105pub_type
杂志文章abstract：:Overexpression of plasminogen activator inhibitor-1 (SERPINE1, PAI-1), the major physiological inhibitor of pericellular plasmin generation, is a significant causative factor in the progression of vascular disorders (e.g. arteriosclerosis, thrombosis, perivascular fibrosis) as well as a biomarker and a predictor of ca...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2008-12-01 00:00:00
abstract：:In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain.We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH14-04-0305
更新日期：2015-03-01 00:00:00
abstract：:DX-9065a is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). We evaluated the effects of DX-9065a and warfarin on bleeding time and blood loss in rat tail transection model and on blood loss in hydrochloride (HCl)-induced rat gastrointestinal haemorrhage m...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
abstract：:Human platelets were separated into subpopulations using continuous flow electrophoresis, which uses electrophoretic mobility as the separative parameter. The platelets with the greatest electrophoretic mobility showed higher amounts of total sialic acid than the less electrophoretically mobile subpopulation (74.3 +/-...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-01-11 00:00:00
abstract：:Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type plasminogen activators. Enhanced levels of PAI-1 are related to pathological conditions associated with hypoxia or hyperinsulinemia. In this study, we investigated the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-08-01 00:00:00
abstract：:When adenosine diphosphate (ADP) is added to hirudinized platelet-rich plasma (PRP) in which the level of platelet cAMP has been pharmacologically elevated, there is an initial rapid fall in the level of cAMP brought about by inhibition of adenylate cyclase. This may be followed by a subsequent activation of adenylate...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:We studied a murine monoclonal antibody (211 A6) to von Willebrand factor (vWF) with a view to investigating structure-relationship of plasma vWF. The specificity of this antibody has been substantiated by ELISA tests and indirect immunofluorescence. It reacts with purified vWF, normal plasma but not with plasma or pl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-06-03 00:00:00
abstract：:Platelet aggregation and fibrinogen binding in whole blood, induced either by ADP or by a 14 amino acid peptide mimicking an N-terminal region of the platelet thrombin receptor (TRP, thrombin receptor activating peptide), have been studied with blood from different species. Aggregation was assessed by counting the num...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:Recently we prepared sulfated, low-molecular-weight lignins (LMWLs) to mimic the biological activities of heparin and heparan sulfate. Chemo-enzymatically prepared sulfated LMWLs represent a library of diverse non-sugar, aromatic molecules with structures radically different from the heparins, and have been found to p...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-07-0454
更新日期：2010-03-01 00:00:00
abstract：:This study was carried out in order to compare the coagulation balance in patients with colorectal cancer before and after surgical removal of tumor with an age matched non-malignancy control group. Furthermore, it was studied whether preoperative coagulation state in cancer patients was correlated to the postoperativ...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:It was the aim of the present study to perform a systematic review of the published studies that estimated the prevalence of non-responders to aspirin, as assessed by the closure time of PFA-100, a point-of-care device, and to analyse: 1) some major clinical and methodological factors that can influence it and 2) its ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH07-08-0530
更新日期：2008-01-01 00:00:00
abstract：:Elevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (> or = 5% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH07-08-0523
更新日期：2008-02-01 00:00:00
abstract：:The etiology and pathophysiology of cerebral sinus venous thrombosis (CSVT) in the paediatric population is still poorly understood, and the role of thrombophilic risk factors remains to be elucidated. In our multi-center case-controlled study we studied 46 patients with CSVT diagnosed from April 1996 to December 2003...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH04-03-0182
更新日期：2004-10-01 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：:Tissue factor (TF) markedly enhances the ability of factor VIIa (FVIIa) to cleave both macromolecular and small peptidyl substrates. Using soluble mutant TF (sTF) to investigate TF-enhanced FVIIa amidolytic activity in solution, we screened thirty-four commercially available peptidyl-p-nitroanilide substrates and foun...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-12-20 00:00:00
abstract：:To investigate the inhibitory mechanism of tissue factor pathway inhibitor (TFPI), an attempt was made to examine the inhibitory activity of TFPI toward the factor VIIa-truncated tissue factor (TF1-219) complex, which lacks its transmembrane and cytoplasmic domains. Factor VIIa-TF1-219 activity was significantly inhib...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:We performed experiments to determine whether endothelial cells synthesize phospholipid metabolites via the lipoxygenase pathway and whether these metabolites influence platelet/vessel wall interactions. Monolayers of cultured human endothelial cells were incubated with 14C-arachidonic acid and their cyclo-oxygenase a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-06-24 00:00:00
abstract：:Erythropoietin has shown to be effective in the correction of the hemostatic defect present in uremic patients. We have investigated the possible effect of recombinant human erythropoietin (rHuEPO) on the signaling processes occurring in platelets. Platelet suspensions were obtained from hemodialyzed patients before a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors o...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0039-1679939
更新日期：2019-05-01 00:00:00
abstract：:Atherosclerosis is at least in part an inflammatory disease. CD14 is an endotoxin receptor that after binding of lipopolysaccharides evokes endothelial activation and secretion of several cytokines. A polymorphism of CD14 has been associated with myocardial infarction. We evaluated the role of the -159 T/C polymorphis...
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/TH03-11-0668
更新日期：2004-05-01 00:00:00
abstract：:Underlying disorders of the coagulation system such as inhibitor deficiencies or decreased fibrinolysis are common in patients suffering from venous thrombosis. They may lead to the necessity of a lifelong prophylaxis. Prompt diagnosis is obviously to the patients benefit. We investigated 22 patients suffering from ve...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:Isolated rat hepatocytes possess per cell 4,500 high-affinity binding sites for thrombin with a Kd of 30-40 pM, and 2.8 X 10(5) low-affinity sites with a Kd of 30 nM. These binding sites are highly specific for thrombin. Half-maximal binding of 125I-labelled thrombin is achieved after 3 min at 37 degrees C and 7 min a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-12-22 00:00:00
abstract：:Hemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels greater than 300 mug/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of throm...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1976-08-31 00:00:00
abstract：:The prevention and treatment of venous thromboembolism (VTE) remains a clinical challenge, primarily owing to drawbacks associated with the use of heparins and vitamin K antagonists (VKAs). These and other factors, including a growing elderly population, mean that VTE presents a continuing burden to patients and physi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,meta分析,评审
doi：10.1160/TH14-06-0484
更新日期：2015-02-01 00:00:00
abstract：:Haemophilia A and B are X-linked disorders which are due to a reduced activity of coagulation factor VIII or IX, respectively. Female carriers have a wide range of plasma concentration of factor VIII or factor IX, and may in rare cases have an affected phenotype. In order to investigate if this variation is related to...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：:There is increasing concern that some anticoagulants can paradoxically increase thrombogenesis under certain circumstances. Previously, we demonstrated that at certain doses a direct thrombin inhibitor, melagatran, worsens the coagulation status induced by tissue factor (TF) injection in a rat model. We utilised an i...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-06-0382
更新日期：2011-12-01 00:00:00
abstract：:Recombinant factor VIIa (rVIIa) has been reported to be clinically effective and safe in haemophilic patients with inhibitor antibodies. Compared to activated prothrombin complex concentrates the risk of thrombotic complications seems to be very low after rVIIa administration. Determination of free thrombin generation...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:Previously, we demonstrated in a rat model of heparin-induced osteoporosis that low molecular weight heparin (LMWH) produces less bone loss than unfractionated heparin, and that only heparin increases osteoclast number and activity. In contrast, both heparin and LMWH were found to decrease osteoblast function to a sim...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:Fourteen patients diagnosed as having thrombotic thrombocytopenia purpura (TTP) were studied. Those who survived have been followed during a 1 to 7 year period. The clinical diagnosis was based on changing neurological findings, thrombocytopenia and evidence of microangiopathic hemolytic anemia. Laboratory tests inclu...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-08-30 00:00:00
