Abstract:
:Tissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Adp inhibits inflammatory cytokine and adhesion molecules expression, and it can prevent endothelial dysfunction. In this study, we investigated the effects of Adp on tumor necrosis factor-alpha (TNF-alpha)-induced expression of TF and TFPI in human umbilical vein endothelial cells (HUVECs), and the signaling transduction pathways involved. It was found that Adp significantly inhibited both TF protein expression and activity in TNF-alpha-stimulated HUVECs. In the meanwhile, it increased TFPI protein expression and activity for about two folds. Adp also inhibited TF mRNA expression induced by TNF-alpha, but had no effect on TFPI mRNA expression. The inhibitory effect of Adp on TNF-alpha-induced TF expression was prevented by pretreatment with Rp-cAMPs, a PKA inhibitor. Adp increased intracellular cAMP content and PKA activity levels in a dose-dependent manner. Phosphorylation of IkappaB-alpha was decreased by Adp, but phosphorylation of p44/42 MAPK, SAPK/JNK, and p38 MAPK were not affected. These results suggested that Adp inhibits TF expression through inhibition of a PKA dependent nuclear factor-kappaB (NF-kappaB) signaling pathway. It was also found that adiponectin promoted Akt and AMP-activated protein kinase phosphorylation. The inhibitory effect of Adp on TNF-alpha-induced TF synthesis was abrogated in part by pretreatment with the PI3kinase inhibitor LY294002, suggesting that Akt activation might inhibit TF expression induced by TNF-alpha. The inhibitory effect of Adp is almost completely abrogated by inhibition of both the cAMP/PKA pathway and PI3K/Akt pathway. In conclusion, our data indicated that inhibition of NF-kappaB through stabilization of IkappaB-alpha and activation of Akt phosphorylation may mediate the inhibitory effect of Adp on TF expression; but the enhancement effect of Adp on the TFPI production might occur via translational rather than transcriptional regulation.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Chen YJ,Zhang LQ,Wang GP,Zeng H,Lü B,Shen XL,Jiang ZP,Chen FPsubject
Has Abstractpub_date
2008-08-01 00:00:00pages
291-300issue
2eissn
0340-6245issn
2567-689Xpii
08080291journal_volume
100pub_type
杂志文章abstract::Catheter-directed thrombolysis has gained increasing acceptance for the treatment of patients who present with vascular occlusion; however, intravenous injection may be preferable in selected patients. Recombinant prourokinase (r-proUK) is a recently-developed fibrin-selective thrombolytic agent with specificity for c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::We evaluated the effect of d-alpha-tocopherol (vitamin E) on the production of prostacyclin (PGI2) by cultured bovine aortic endothelial cells. Vitamin E at physiological doses significantly enhanced the production of PGI2 by aortic endothelial cells when added to the culture simultaneously with histamine, the Ca2+ io...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-12-07 00:00:00
abstract::Using gain-of-function factor IX (FIX) for replacement therapy for haemophilia B (HB) is an attractive strategy. We previously reported a high-activity FIX, FIX-Triple (FIX-V86A/E277A/R338A) as a good substitute for FIX-WT (wild-type) in protein replacement therapy, gene therapy, and cell therapy. Here we generated a ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-02-0154
更新日期:2013-08-01 00:00:00
abstract::Venous thromboembolism (VTE) is a central concern in the intensive care unit (ICU). However, little is known about both current practices for VTE prevention in the ICU and the risk for VTE in persons with severe sepsis and septic shock. XPRESS was a randomized, double-blind, placebo-controlled trial of prophylactic he...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2009-01-01 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::A high throughput 384-well plate assay of blood function in 60 microl reactions with the fluorogenic thrombin substrate, boc-VPR-MCA, allowed for real-time monitoring of coagulation under a diverse set of reaction conditions. Using recalcified, citrated whole blood diluted 3-fold with corn trypsin inhibitor (to block ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-03-0154
更新日期:2004-10-01 00:00:00
abstract::Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size> 5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative proteomic analysis of plas...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-10-0874
更新日期:2015-06-01 00:00:00
abstract::The antithrombotic effect of MCI-9042, (+-)-2-(dimethyl-amino)-1-((o-(m- methoxyphenethyl)phenoxyl]methyl]ethyl hydrogen succinate hydrochloride was investigated in three different experimental thrombosis models in animals. Simultaneous injection of serotonin and collagen into the tail vein in mice induced acute pulmo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Antiphospholipid antibodies (aPL) have been associated with thrombosis and pregnancy losses in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. It has been proposed that aPL may affect endothelia...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVE:To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. DESIGN:Multicentre, open-label, single arm, phase...
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:1998-12-01 00:00:00
abstract::Both the HEPTEST and amidolytic anti factor Xa assays are currently being used for heparin activity detection in plasma from patients receiving standard heparin or low molecular weight heparin (LMWH). In this study we have investigated the influence of recombinant and endogenous Tissue Factor Pathway Inhibitor (TFPI) ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-09-07 00:00:00
abstract::Hemorrhagic diathesis and widespread microthrombosis are common in heatstroke. To assess the early stages of coagulopathy in heatstroke, thrombin-antithrombin III (TAT), fibrin monomers, plasmin-alpha 2-antiplasmin (PAP), plasminogen and D-Dimer were measured in 16 heatstroke patients (means +/- SE rectal temperature ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-12-01 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::It was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/TH16-09-0728
更新日期:2017-04-03 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::In an international collaborative study three candidate reference and the local APTT reagent have been tested with lyophilized plasmas containing heparin added in vitro and fresh plasmas from heparinized patients to determine whether it was possible to standardize APTT heparin monitoring. The APTT responses of patient...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:
更新日期:1995-01-01 00:00:00
abstract::The vast majority of thrombin (>95%) is generated after clotting is completed, suggesting that thrombin formation serves purposes beyond coagulation, such as tissue repair after vessel injury. Two types of vascular thrombin binding sites exist: protease-activated receptors (PARs) and thrombomodulin (TM). Their express...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH09-09-0627
更新日期:2010-05-01 00:00:00
abstract::Ultra-low-molecular-weight heparins (ULMWHs) with better efficacy and safety ratios are under development; however, there are few structural data available. The main structural features and molecular weight of ULMWHs were studied and compared to enoxaparin. Their monosaccharide composition and average molecular weight...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-11-0795
更新日期:2013-03-01 00:00:00
abstract::Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved in host defence du...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-12-0920
更新日期:2017-07-26 00:00:00
abstract::Probands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enz...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-11-24 00:00:00
abstract::The evidence is reviewed and a model presented for two distinct receptors being involved in platelet activation induced by alpha-thrombin: a high affinity thrombin receptor constituting approximately 50 copies of a supercomplexed form of GPIb coupled to phospholipase A2 and a moderate affinity receptor constituting ap...
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::Ridogrel (6.3 x 10(-6) to 10(-4) M) inhibited contractions of isolated rat caudal arteries and rabbit femoral arteries caused by U-46619. The slope of an Arunlakshana-Schild plot (pA2-value: 3.4 x 10(-6) M) on the caudal artery was slightly higher than one (1.14). This effect was maximal within 20 min of incubation of...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-08-13 00:00:00
abstract::To identify whether genotype contributes to the difference in PAI-1 levels in type 1 and type 2 diabetic subjects and whether genotype relates to the development of retinopathy, a Hind III restriction fragment length polymorphism and two dinucleotide repeat polymorphisms were studied. In 519 Caucasian diabetic subject...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-06-01 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::In this review the interaction between invasive human pathogens expressing plasmin(ogen) receptors and/or producing plasminogen activators with the human plasmin(ogen) system is described. Evidence is presented for multiple mechanisms by which human pathogens can acquire a surface bound form of plasmin that cannot be ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1997-01-01 00:00:00
abstract::A factor VIII inhibitor has been found in a patient with an unusual combination of factor VIII-related properties. The inhibitor is directed specifically against the clotting activity (VIII:C) of the factor VIII complex. It behaves in a similar fashion to high responding inhibitors of factor VIII seen in haemophilia A...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-04-30 00:00:00
abstract::Defibrotide is an antithrombotic drug which enhances prostacyclin production and activates fibrinolytic system. The aim of this study was to investigate the improvement of walking distance in patients with intermittent claudication treated with defibrotide. DICLIS was a double blind, placebo-controlled study which inc...
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:2000-05-01 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::An algal sulfated galactan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant action is due to promoting thrombin and factor (F)Xa inhibition by antithrombin and heparin cofactor II. Here, we evaluated the anticoagulant effect of the algal sulfated galactan using serpin-free plasm...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-04-0273
更新日期:2009-12-01 00:00:00
abstract::Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis. As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-04-0216
更新日期:2011-03-01 00:00:00