Abstract：
:In the past decade understanding of the role of the Rho GTPases RhoA, Rac1 and Cdc42 has been developed from regulatory proteins that regulate specific actin cytoskeletal structures - stress fibers, lamellipodia and filopodia - to complex integrators of cytoskeletal structures that can exert multiple functions depending on the cellular context. Fundamental to these functions are three-dimensional complexes between the individual Rho GTPases, their specific activators (GEFs) and inhibitors (GDIs and GAPs), which greatly outnumber the Rho GTPases themselves, and additional regulatory proteins. By this complexity of regulation different vasoactive mediators can induce various cytoskeletal structures that enable the endothelial cell (EC) to respond adequately. In this review we have focused on this complexity and the consequences of Rho GTPase regulation for endothelial barrier function. The permeability inducers thrombin and VEGF are presented as examples of G-protein coupled receptor- and tyrosine kinase receptor-mediated Rho GTPase activation, respectively. These mediators induce complex but markedly different networks of activators, inhibitors and effectors of Rho GTPases, which alter the endothelial barrier function. An interesting feature in this regulation is that Rho GTPases often have both barrier-protecting and barrier-disturbing functions. While Rac1 enforces the endothelial junctions, it becomes part of a barrier-disturbing mechanism as activator of reactive oxygen species generating NADPH oxidase. Similarly RhoA is protective under basal conditions, but becomes involved in barrier dysfunction after activation of ECs by thrombin. The challenge and promise lies in unfolding this complex regulation, as this will provide leads for new therapeutic opportunities.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Beckers CM,van Hinsbergh VW,van Nieuw Amerongen GPdoi
10.1160/TH09-06-0403subject
Has Abstractpub_date
2010-01-01 00:00:00pages
40-55issue
1eissn
0340-6245issn
2567-689Xpii
09-06-0403journal_volume
103pub_type
杂志文章,评审abstract：:This study was performed to follow up on the observation that gelatinase A (MMP-2) deficiency impairs adipose tissue development in mice. The aim was to evaluate the role of its functional homologue gelatinase B (MMP-9) in adipose tissue growth. MMP-9 antigen levels were determined in lean and in obese women before an...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-10-0739
更新日期：2010-07-01 00:00:00
abstract：:Background Polycystic ovarian syndrome (PCOS) affects up to 18% of reproductive-aged women with increased risks of cardiovascular disease and venous thromboembolic disease, related to metabolic and hormonal features, obesity and an apparent hypofibrinolytic state, possibly exacerbated by current PCOS treatments. Objec...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-04-0248
更新日期：2017-11-01 00:00:00
abstract：:A significant proportion of patients with Essential Thrombocythaemia (ET) have thrombotic complications which have an important impact upon the quality, and duration of their life. We performed a retrospective cross sectional study of the prevalence of antiphospholipid antibodies (APA) in 68 ET patients. Compared to 2...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-05-01 00:00:00
abstract：:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pretransplant genetic susceptibility is evident in adult TA-TMA and further investigated the association of TMA-associated variants with clinical out...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1702225
更新日期：2020-04-01 00:00:00
abstract：:Following the initial report of the clinical use of plasminogen activators (PAs) in cerebrovascular thrombosis in 1958, interest in the efficacy of this approach accelerated only when the need for acute intervention in stroke was recognized. The use of PAs in acute ischemic stroke is based on the observation that appr...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
abstract：:A preliminary clinical trial was conducted to determine the feasibility of achieving and regulating therapeutic anticoagulation with heparin given by continuous subcutaneous infusion. Five patients with deep venous thrombosis confirmed by impedance plethysmography and/or venography were studied. All patients received ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-02-26 00:00:00
abstract：:Tamoxifen is a known anti-cancer drug and established estrogen receptor modulator. Few clinical studies have earlier implicated the drug in thrombotic complications attributable to lower anti-thrombin and protein S levels in plasma. However, action of tamoxifen on platelet signalling machinery has not been elucidated ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-03-0178
更新日期：2011-10-01 00:00:00
abstract：:Bleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine less than 300 mumol/l), moderate (300-600 mumol/l) or severe rena...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-08-30 00:00:00
abstract：:It is now recognised that acute myocardial infarction results from the rupture of atherosclerotic plaques. Lymphocytes and macrophages, which infiltrate rupture sites, contribute to plaque degradation by expressing urokinase (u-PA) bound to cell membrane by urokinase receptor (u-PAR) and by secreting metalloproteinase...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：:Previous studies have demonstrated that cell-permeable cytoplasmic tail (CT) alpha(II)beta peptides can modulate the activation of alpha(IIb)b(3). As alpha(V) CT contains an alpha(II)beta homologous region, a series of cell-permeable alpha(V) and alpha(IIb) peptides were generated to determine if alpha(V) CT can modul...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH07-08-0498
更新日期：2008-01-01 00:00:00
abstract：:We investigated the prevalence of the new recently reported mutation in the prothrombin gene (20210 A) in a sample of 116 unrelated patients with venous thromboembolism. We found 20 heterozygous carriers (17.2%, CI 95% 10.4-21.1). In comparison, we observed 13 carriers among 201 healthy unmatched controls (6.5%, CI 3....
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:Tissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-08-24 00:00:00
abstract：:Constitutive expression of tissue factor (TF) by acute promyelocytic leukemia (APL) cells may contribute to thrombotic complications. In this study we examined the transcriptional mechanisms of all-trans retinoic acid (ATRA)-induced down-regulation of TF in the APL cell line NB4, by analysis of stable clones expressin...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-02-0087
更新日期：2003-11-01 00:00:00
abstract：:Hematological parameters including platelet counts, etc. were determined in 1,140 healthy subjects living in four cities: Suzhou (Jiangsu Province), Chengdu (Sichuan Province) and Harbin (Heilongjang Province) in China, and Kobe in Japan. Then, the reference intervals for platelet counts were calculated and compared. ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
abstract：:Tissue factor (TF) plays a critical role in tumour growth and metastasis, and its enhanced release into plasma in association with cellular microparticles (MPs) has recently been associated with pathological cancer progression. We have previously demonstrated significantly elevated levels of plasma TF antigen as well ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2009-06-01 00:00:00
abstract：:This study was performed to assess the prevalence of deep vein thrombosis (DVT) in consecutive obstetric patients with clinical symptoms of DVT, using impedance plethysmography (IPG) as the diagnostic method and to establish the safety of withholding anticoagulant therapy in patients with a repeatedly normal IPG. In a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-01-23 00:00:00
abstract：:Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the TF-dependent coagulation system. In meningococcal disease, up-regulation of tissue factor expression on blood monocytes and possibly on endothelial cells has the potential to trigger the activation of the TF-dependent pathway of coagulation. Intravasc...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:Prevention of a secondary response to factor IX by cyclophosphamide was attempted in an 11 year old patient with severe Christmas disease. An antibody to factor IX had been present for 4 years before immunosuppressive therapy was tried. Despite profound lymphopenia, synthesis of factor IX antibody was not depressed. T...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1976-08-31 00:00:00
abstract：:In two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The firs...
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：1986-12-15 00:00:00
abstract：:The endothelial barrier of the vasculature is of utmost importance for separating the blood stream from underlying tissues. This barrier is formed by tight and adherens junctions (TJ and AJ) that form intercellular endothelial contacts. TJ and AJ are integral membrane structures that are connected to the actin cytoske...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH14-04-0298
更新日期：2015-01-01 00:00:00
abstract：:Heparin-induced thrombocytopenia (HIT), a relatively common complication of heparin therapy, results of platelet activation, via the receptor for the Fc domain of IgG (FcgammaRIIa), by heparin-dependent-antibodies, commonly directed against the heparin-platelet factor 4 (H-PF4) antigenic complex. Our strategy was to u...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
abstract：:Coagulation factor III (tissue factor) is required for significant activation of factor X in the presence of factor VIIa. Factor III is a membrane protein which requires bound phospholipids for activity, and removal of lipids during purification of factor III abolishes its activity. The activity can be recovered if li...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-08-29 00:00:00
abstract：:Although there is considerable variability of platelet reactivity among patients treated with clopidogrel, little is known about inter-individual differences and possible role of proton pump inhibitors (PPIs) after prasugrel. We defined the extent of inter-patient variability, and evaluated the impact of PPI interacti...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH11-09-0622
更新日期：2012-02-01 00:00:00
abstract：:The alphaII(b)beta3 integrin and FcgammaRII receptors mediate, respectively, platelet adhesion and spreading on fibrinogen and immunoglobulin (IgG) coated surfaces. Platelet adhesion to fibrinogen resulted in a partial conversion of the faster to the slower migrating (phosphorylated) form of Ca(+2)-sensitive cytosolic...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:The demographic and clinical characteristics of adults and children with lower extremity deep-vein thrombosis and/or pulmonary embolism (LE DVT/PE) may differ from those with abdominal vein thrombosis (abdominal VT). Abdominal VT can be a presenting sign of an underlying prothrombotic state, and its presence in the se...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH12-08-0568
更新日期：2013-04-01 00:00:00
abstract：:Abnormalities of Hageman factor dependent pathways have been described in a wide variety of human disease states. Congenital deficiencies of factor XII (Hageman trait) prekallikrein (Fletcher trait) and high molecular weight kininogen (Williams, Fitzgerald and Flaujeac traits) although resulting in profound in vitro c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1977-12-15 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：:The molecular basis of Factor V deficiency has been defined in few patients only. We report a homozygous nucleotide change (G6395A) in two Tunisian probands with Factor V deficiency and bleeding episodes. This substitution results in the replacement of an arginine (R) by a histidine (H) in amino acid position 2074, lo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2002-02-01 00:00:00
abstract：BACKGROUND:Measurements of prothrombin fragment 1+2 (F1+2), thrombin antithrombin III complexes (TAT) and D-dimer plasma levels have been proposed as non-invasive screening tests to exclude postoperative deep venous thrombosis (DVT). We investigated the diagnostic efficacy of these coagulation activation markers to rul...
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：1998-03-01 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
