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 umbilical vein endothelial cells (HUVEC), and monitored detachment, viability, caspase activation and signaling. CH1 expression induced dose-dependent cell detachment. At 24 h over 90% of CH1-expressing HUVEC were detached but largely viable (>85%). No evidence of pro-caspase-8,-3, and PARP cleavage or suppression of phosphorylation of ERK, PKB and Ikappa-B was observed. The caspase inhibitor z-VAD did not prevent cell detachment. At 48 h, however, CH1-expressing cells were over 50% dead. As a comparison trypsin-mediated detachment resulted in a time-dependent cell death, paralleled by caspase-3 activation and suppression of ERK, PKB and Ikappa-B phosphoyrylation at 24 h or later after detachment. HUVEC stimulation with agents that strengthen integrin-mediated adhesion (i.e. PMA, the Src inhibitor PP2 and COMP-Ang1) did not prevent CH1-induced detachment. Expression of CH1 in rat carotid artery endothelial cells in vivo caused endothelial cell detachment and increased nuclear DNA fragmentation among detached cells. A construct lacking the integrin cytoplasmic domain (CH2) had no effect on adhesion and cell viability in vitro and in vivo. These results demonstrate that isolated beta1 cytoplasmic domain expression induces caspase-independent detachment of viable endothelial cells and that death is secondary to detachment (i.e. anoikis). They also reveal an essential role for integrins in the adhesion and survival of quiescent endothelial cells in vivo.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Hasmim M,Vassalli G,Alghisi GC,Bamat J,Ponsonnet L,Bieler G,Bonnard C,Paroz C,Oguey D,Rüegg Ckeywords:
subject
Has Abstractpub_date
2005-11-01 00:00:00pages
1060-70issue
5eissn
0340-6245issn
2567-689Xpii
05111060journal_volume
94pub_type
杂志文章abstract::We have developed a simple assay that measures the circulating activated protein C (APC) in plasma. The assay requires collection of duplicate blood samples, one in citrate plus heparin and the other in citrate plus inhibitors of the enzyme. In the heparin tube, APC reacts completely and irreversibly with its major pl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Following exposure of rats to graded doses of fresh cigarette smoke, the aortic endothelium examined by scanning electron microscopy regularly showed alterations. These essentially consisted of areas of blebbing and microvillus-like projections from the luminal surface, and the presence in the majority of cases, of mi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-10-29 00:00:00
abstract::von Willebrand disease (VWD) is a quantitative or qualitative defect in von Willebrand factor (VWF) resulting in mucocutaneous bleeding symptoms and hemorrhage following hemostatic challenges, such as trauma or surgery. VWD-specific therapy, DDAVP (1-desamino-8-D-arginine vasopressin) and VWF concentrates, is necessar...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1713636
更新日期:2020-08-01 00:00:00
abstract::Using an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::In this study, the clot accumulation properties of liposome-coupled plasminogen were compared to those of free (non-liposomal) plasminogen in an in vitro, closed-loop, flow-system. After introduction of a clot into the closed system, double-radiolabelled plasminogen-liposomes were administered and the accumulation of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::The effect of the ADP receptor antagonists ATP and adenosine 5'-(beta, gamma-methylene)triphosphate (AMP-PCP), and the ADP-utilizing enzyme systems creatine phosphokinase/creatine phosphate (CPK/CP) and pyruvate kinase/phosphoenol pyruvate (PK/PEP) on platelet deposition onto type I collagen was examined. An in vitro ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-04-02 00:00:00
abstract::Antithrombin III (ATIII) deficiency is one of the few known abnormalities of the coagulation system known to predispose to venous thromboembolism but its relation to arterial disease is not established. We describe two related patients with this disorder, both of whom suffered arterial thrombotic events, at an early a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-02-19 00:00:00
abstract::A new genetic test has been developed for detection of the mutation known as factor V Leiden. The test employs heteroduplex technology and comprises a single PCR reaction followed immediately by PCR product analysis. It therefore represents the minimum practical route from blood/tissue sample to genetic result. A coho...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Heparin is one of the oldest biological medicines, and has an established place in the prevention and treatment of venous thrombosis. Low-molecular-weight heparins (LMWH) have been developed by several manufacturers and have advantages in terms of pharmacokinetics and convenience of administration. They have been show...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH08-01-0032
更新日期:2008-05-01 00:00:00
abstract::Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1648251
更新日期:2018-06-01 00:00:00
abstract::We have developed a sensitive and quantitative RT-PCR assay for the determination of tissue factor (TF) mRNA levels in human cells. An in vitro synthesized internal standard RNA was used to correct for differences in reverse transcription or amplification of various RNA samples. The PCR products were quantitated by hy...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-11-10 00:00:00
abstract::Meseclazone and its major metabolite, 5-chlorosalicylic acid (5-CSA) have been shown to possess anti-inflammatory, analgesic and antipyretic activity. The comparative effects of these compounds on pletelet aggregation were evaluated in vitro and ex vivo with acetylsalicylic acid (ASA). In vitro, meseclazone and ASA ex...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-08-31 00:00:00
abstract::A new immunoadsorbent-amidolytic assay (IAA) for the specific differential detection of two-chain urokinase-type plasminogen activator (tcu-PA) and its single-chain precursor (scu-PA) in cell culture supernatants has been developed. The assay combines the selectivity of immunoassays with the specificity of enzyme acti...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-12-15 00:00:00
abstract::Alpha 2-macroglobulin (alpha 2 M) in vitro inhibits numerous proteinases that are generated during inflammatory reactions and therefore, probably plays an important role in diseases such as sepsis. To monitor the state of alpha 2 M in sepsis, we developed novel assays for functional and inactive alpha 2M. Functional a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-01-23 00:00:00
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 fibrinolyti...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-12-0944
更新日期:2013-06-01 00:00:00
abstract::A previous study of neurosurgical patients demonstrated an imbalance between thrombin and plasmin action following surgery. The present study was designed to determine the effect of intermittent pneumatic calf compression on postoperative enzyme activity. Fibrinopeptide A (FPA) and B beta 1-42 levels, reflecting throm...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-10-21 00:00:00
abstract::At the moment of hemostasis, the platelet must be able to reorganize its cytoskeleton through a complexly orchestrated signaling cascade that is regulated, in part, by polyphosphoinositides. In the past 6 years, evidence has accumulated that PH domains bind these polyphosphoinositides and play a role in cytoskeletal c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-08-01 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::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::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::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::Warfarin induction is accomplished by titrating dosage to coagulation test results. Algorithms can guide this process but not identify the starting dose. We hypothesized that an initial warfarin dose approximating the maintenance value would safely enhance rapidity of induction. In a randomized trial we compared a fix...
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:
更新日期:2003-02-01 00:00:00
abstract::In vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 micrograms rt-PA/ml blood (3.4 micrograms/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-10-28 00:00:00
abstract::D-Dimer measurements are being increasingly used for negative prediction of deep vein thrombosis (DVT). At our institution, clinical score, D-Dimer assay, plethysmography and, if necessary, Doppler ultrasound are used to secure the diagnosis. We collected the data from 100 consecutive patients proven to have DVT. We e...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-11-0699
更新日期:2004-06-01 00:00:00
abstract::Patients with diabetes display increased platelet activation. Recent data show a markedly increased risk for cardiovascular events already in pre-diabetic individuals with impaired glucose tolerance (IGT). We investigated whether IGT is associated with platelet activation. Blood samples were collected from young lean ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-02-0118
更新日期:2004-07-01 00:00:00
abstract::Excessive leukocyte infiltration causes severe tissue damage in a variety of inflammatory diseases. The initial step in leukocyte extravasation is mediated by selectins and oligosaccharides on their glycoconjugate ligands. Human milk is a rich source of lactose-derived oligosaccharides that are partly absorbed in the ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-01-0055
更新日期:2004-12-01 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::To add an increased level of safety to antihemophilic factor replacement therapy, a full-length, recombinant Factor VIII (rFVIII) product has been developed without human-derived plasma proteins during purification and formulation and using an additional solvent/detergent viral inactivation step. This first clinical t...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2000-06-01 00:00:00
abstract::Recombinant human activated factor VII (rHuFVIIa) can reduce bleeding but may be associated with arterial thrombosis. We hypothesized that rHuFVIIa would increase the occurrence of cyclic flow reductions (CFR) and reduce intra-abdominal bleeding in an experimental model. An adapted Folts' model of carotid artery lesio...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-02-01 00:00:00