Abstract:
:It is conceivable that the extent and spatio-temperal expression of dozens or even a few hundred genes are significantly altered during the development and progression of atherosclerosis as compared to normal circumstances. Differential gene expression in vascular cells and in blood cells, due to gene-gene and gene-environment interactions can be considered the molecular basis for this disease. To comprehend the coherence of the complex genetic response to systemic and local atherosclerotic challenges, one needs accessible high through-put technologies to analyze a panel of differentially expressed genes and to describe the interactions between and among their gene products. Fortunately, new technologies have been developed which allow a complete inventory of differential gene expression, i.e. DD/RT-PCR, SAGE and DNA micro-array. The initial data on the application of these technologies in cardiovascular research are now being reported. This review summarizes a number of key observations. Special attention is paid to a few central transcription factors which are differentially expressed in endothelial cells, smooth muscle cells or monocytes/ macrophages. Recent data on the role of nuclear factor-kappaB (NF-kappaB) and peroxisome proliferation-activating receptors (PPARs) are discussed. Like the PPARs, the NGFI-B subfamily of orphan receptors (TR3, MINOR and NOT) also belongs to the steroid/thryroid hormone receptor superfamily of transcription factors. We report that this subfamily is specifically induced in a sub-population of neointimal smooth muscle cells. Furthermore, intriguing new data implicating the Sp/XKLF family of transcription factors in cell-cell communication and maintenance of the atherogenic phenotype are mentioned. A member of the Sp/XKLF family, the shear stress-regulated lung Krüppel-like factor (LKLF) is speculated to be instrumental for the communication between endothelial cells and smooth muscle cells. Taken together, the expectation is that the fundamental knowledge obtained on atherogenesis and the data that will be acquired during the coming decade with the new, powerful high through-put methodologies will lead to novel modalities to treat patients suffering from cardiovascular disease. In view of the phenotypic changes of vascular and blood-borne cells during atherogenesis, therapeutic interventions likely will focus on reversal of an acquired phenotype by gene therapy approach or by using specific drugs which interfere with aberrant gene expression.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Monajemi H,Arkenbout EK,Pannekoek Hkeywords:
subject
Has Abstractpub_date
2001-07-01 00:00:00pages
404-12issue
1eissn
0340-6245issn
2567-689Xpii
01070404journal_volume
86pub_type
杂志文章,评审abstract::We reported previously that plasma fibrinogen was significantly higher in U.S. Caucasians than in Japanese, which may contribute to the higher mortality rate of coronary heart disease in the United States than in Japan. To examine the contribution of genetic variations to the race difference in plasma fibrinogen level...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Integrins are cell surface adhesion receptors that participate in a variety of important processes throughout the vasculature. Here we summarize some recent findings on the regulation of integrin mediated cellular adhesion. Particular emphasis is placed on the regulation of integrin affinity for ligand (activation), a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2001-07-01 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::Primary prevention of cardiovascular events with aspirin in patients with elevated cardiovascular risk, including diabetics, is currently under intense discussion. Data from meta-analyses suggests that the efficacy of aspirin in these patients is low, whereas there is a significantly increased bleeding tendency. Howev...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0039-1694774
更新日期:2019-10-01 00:00:00
abstract::Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to co...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/TH10-05-0327
更新日期:2011-03-01 00:00:00
abstract::Factor X (FX) is a vitamin K-dependent serine protease zymogen that functions in both the extrinsic and intrinsic pathways of blood coagulation. In this study, the 5'-flanking region of the murine FX gene was analyzed to determine those elements that govern its transcriptional activity and regulation. Consistent with ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Heparin and low molecular weight heparins stimulate two to three fold the accumulation of an antithrombotic heparan sulfate secreted by endothelial cells in culture. This led us to search for the minimum structural requirements of the heparin molecule able to elicit the enhancement of the heparan sulfate. Fragments we...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::Thirty-three patients with acute iliofemoral thrombosis were randomly assigned to three treatment groups in a pilot dose-ranging study of thrombolytic therapy in deep vein thrombosis. One group received tissue culture urokinase in a dose of 2,200 I.U./kg/hr, and a second group in a dose of 1,100 I.U./kg/hr following a...
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:1983-10-31 00:00:00
abstract::Although there is evidence that altitude increases the platelet count, its effect on the platelet precursor stimulating factor, thrombopoietin (TPO), is unclear. Unlike erythropoietin, TPO appears largely unresponsive to exogenous signals. In a study in 16 healthy volunteers, we report the effects of altitude exposure...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-02-0086
更新日期:2005-01-01 00:00:00
abstract::The mechanism of thrombin induction of tissue- and urokinase-type plasminogen activator (t-PA and u-PA) biosynthesis was investigated in cultured human fetal lung fibroblast cells, IMR-90. Northern blot analysis of total RNA from thrombin-treated cells showed marked accumulations of both t-PA and u-PA mRNA during 24 h...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Moderate or severe paravalvular regurgitation after transcatheter aortic valve implantation (TAVI) is frequently associated with a loss of high-molecular-weight multimers of von Willebrand factor (VWF) and a reduced VWF collagen-binding capacity. It is unclear whether this phenomenon can also be observed in patients w...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:10.1160/17-07-0506
更新日期:2018-01-01 00:00:00
abstract::The pharmacokinetics of recombinant tissue factor pathway inhibitor (TFPI) after an intravenous bolus injection was studied in rabbits. Clearance of TFPI was followed by measurement of the radioactivity of the 125I-labelled compound in the whole plasma or the trichloroacetic acid precipitate and by quantitation of the...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-07-06 00:00:00
abstract::The esterase activity of highly purified human urokinase on Nalpha-acetylglycl-L-lysine methyl ester is strongly inhibited by 1 X 10(-5) to 1 X 10(-2)M Cu++, Hg++, Ni++, Co++, Fe+++, and Mn++ solutions, whereas Na+, K+, Ca++, and Mg++ are weakly effective. This inhibition is parallel with the inhibition of activation ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-02-28 00:00:00
abstract::Some classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this "factor VIII bypassing activity". When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-10-31 00:00:00
abstract::Congenital afibrinogenemia and severe hypofibrinogenemia are severe bleeding disorders characterized by either undetectable or very low levels of fibrinogen in patients' plasma and platelets. A majority of the reported cases are caused by mutations in the fibrinogen Aalpha chain. In this study, we identified a genetic...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH06-01-0020
更新日期:2006-06-01 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::Vascular injury in acute coronary syndromes (ACS) involves a complex cross-talk between inflammatory mediators, platelets and thrombosis, where the interaction between platelets and coagulation factors (e. g. thrombin) is a central link between thrombosis and inflammation. In ACS, aspirin at antiplatelet doses exhibit...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH15-03-0191
更新日期:2015-08-31 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::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::Peripheral vascular disease (PVD) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease. Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD, no data are available comparing d...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::The still living members of the original bleeder family on the Aland Islands described by von Willebrand in 1926 have been reinvestigated by using modern laboratory techniques for the measurement of the Factor VIII complex and with regard to platelet aggregation. The low level of F VIII : C activity demonstrated in 19...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-02-23 00:00:00
abstract::Platelet-leukocyte interactions are recognised to have pro-inflammatory effects, which may be important in the pathophysiology of ischaemic heart disease. Clopidogrel and the novel intravenous antithrombotic agent AR-C69931MX act at the level of the platelet P2Y12 receptor, which is known to amplify platelet activatio...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::The Pulmonary Embolism Severity Index (PESI) is a validated clinical prognostic model for patients with acute pulmonary embolism (PE). Our goal was to assess the PESI's inter-rater reliability in patients diagnosed with PE. We prospectively identified consecutive patients diagnosed with PE in the emergency department ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-07-0426
更新日期:2010-12-01 00:00:00
abstract::It has previously been reported that EGF enhances uPA but not tPA in the A431 squamous carcinoma cell line. To determine whether the absence of tPA modulation by EGF reflected steady levels or the action of an anti-activator, we assayed tPA, PAI-1 and tPA/PAI-1 complexes by zymography and immunological assays. Under c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-11-30 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::The endothelial protein C receptor (EPCR) is expressed by trophoblast cells. Mid-gestation pregnancy loss is described in animals with a haemochorial placenta lacking EPCR. The A6936G allele of the EPCR gene (PROCR) may be associated with lower EPCR densities on trophoblasts, but data are lacking for its effect on the...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH-09-04-0224
更新日期:2009-10-01 00:00:00
abstract::Atherosclerotic plaques are found at distinct locations in the arterial system, despite the exposure to systemic risk factors of the entire vascular tree. From the study of arterial bifurcation regions, emerges ample evidence that haemodynamics are involved in the local onset and progression of the atherosclerotic dis...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH15-07-0597
更新日期:2016-03-01 00:00:00
abstract::This study assessed the frequency and factors associated with failure to correct international normalised ratio (INR) in patients administered fresh frozen plasma (FFP) for warfarin-related major bleeding. This retrospective database analysis used electronic health records from an integrated health system. Patients wh...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-09-0646
更新日期:2012-04-01 00:00:00
abstract::One hundred patients were included in a randomized open trial to assess the systemic factor Xa (FXa) and thrombin inhibitory effect as well as the safety profile of low molecular weight heparin (LMWH) given subcutaneously in conjunction with streptokinase (SK) in patients with acute myocardial infarction (MI). The tre...
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:1997-01-01 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