Abstract:
:Atherosclerosis and its clinical manifestations (i.e. myocardial infarction, stroke) are major causes of mortality and morbidity in Western countries. Endothelial dysfunction is considered the first step in the cascade leading up to coronary events. Increasing evidence suggests that direct inhibition of thromboxane A2/prostaglandin (TP)-receptors may not only have anti-platelet effects but also impact endothelial dysfunction as well as inflammatory component of atherosclerosis. While TP-receptor involvement in platelet function has received the greatest attention, more recent findings support the critical role of TP-receptor in other pathophysiological aspects of atherothrombosis. Prostanoids (i.e. TxA2, F2-isoprostanes, prostaglandins endoperoxides PGG2/PGH2) are known to promote the initiation and progression of atherosclerosis, not only via platelet activation, but through leukocyte-endothelial interactions and vasoconstriction. Dysfunctional endothelium, characterised by increased COX-activity, releases prostanoids that promote endothelial exposure to adhesion molecules and induce smooth muscle cell contraction. Plaque macrophages synthesise PGH2/PGG2 via COX-2; these potent prostanoids can trigger platelet activation and aggregation despite COX-1 inhibition by aspirin. TP-receptor inhibition has been reported to exert anti-atherosclerotic effects in pre-clinical model of disease. Reduction of plaque burden was associated with plaque stabilisation documented by the reduction in the content of macrophages, apoptotic cells, MMPs and endothelin-1, and the increase in smooth muscle cells content. TP-receptor blockade might have an anti-atherosclerotic and plaque stabilisation effect. The possibility of combining anti-platelet activity with an anti-atherosclerotic effect via selective TP-receptor inhibitors could have important implications especially in clinical conditions associated with increased production of prostanoids, such as diabetes.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Giannarelli C,Zafar MU,Badimon JJdoi
10.1160/TH10-03-0195subject
Has Abstractpub_date
2010-11-01 00:00:00pages
949-54issue
5eissn
0340-6245issn
2567-689Xpii
10-03-0195journal_volume
104pub_type
杂志文章,评审abstract::Antithrombin (AT) is a protein of the serpin superfamily involved in regulation of the proteolytic activity of the serine proteases of the coagulation system. AT is known to exhibit anti-inflammatory and cardioprotective properties when it binds to heparan sulfate proteoglycans (HSPGs) on vascular cells. AMP-activated...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-04-0360
更新日期:2015-02-01 00:00:00
abstract::Two polymorphisms in the endothelial protein C receptor (EPCR) gene, 4600A/G and 4678G/C, have been reported to influence the risk of venous thromboembolism (VTE). The objective of this study was to assess whether these polymorphisms modify the risk of VTE in carriers of factor V (FV) Leiden. We genotyped 295 carriers...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-02-0089
更新日期:2005-08-01 00:00:00
abstract::Elucidation of the molecular defects responsible for antithrombin III deficiency is proceeding rapidly. In order that a record is kept of the new and duplicated mutations that are found, we have compiled a database that we plan to update annually. In this, the first report of the database, we list 6 antithrombin III l...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-12-02 00:00:00
abstract::Activated protein C resistance is in almost all cases caused by the factor V Leiden mutation (FV:R506Q). Due to the high prevalence and clinical significance of the mutation reliable methods suited for processing large sets of samples are in demand. We here present the oligonucleotide ligation assay (OLA) with lanthan...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::Increased liver fat may be caused by insulin resistance and adipose tissue inflammation or by the common I148M variant in PNPLA3 at rs738409, which lacks both of these features. We hypothesised that obesity/insulin resistance rather than liver fat increases circulating coagulation factor activities. We measured plasma...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-09-0716
更新日期:2017-01-26 00:00:00
abstract::Developmental haemostasis is a concept, now universally accepted, introduced by Andrew et al. in the late 1980's. However, coagulation analysers and reagents have changed significantly over the past 15 years. Coagulation testing is known to be sensitive to changes in individual reagents and analysers. We hypothesised ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-01-0047
更新日期:2006-02-01 00:00:00
abstract::The PAI-1 gene promoter 4G/5G polymorphism was found to be associated with plasma PAI-1 activity in Northern and Central Europe populations, but no data are available on the association between this polymorphism and PAI-1 levels in Southern Europe countries (such as Italy) where the incidence of ischemic disorders is ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::The cofactor tetrahydrobiopterin (BH4) is required for nitric oxide (NO) production by all nitric oxide synthase (NOS) enzymes and is a key regulator of cellular redox signalling. When BH4 levels become limiting NOS enzymes become 'uncoupled' and produce superoxide rather than NO. Endothelial cell BH4 is required for ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH12-06-0424
更新日期:2012-11-01 00:00:00
abstract::The introduction of venography into patient care was a major advance because it was the first accurate method for the diagnosis of DVT. Compression ultrasound has since become the preferred test for patients with suspected DVT because, unlike venography, it is simple, non-invasive and widely available. Venography has ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH13-07-0562
更新日期:2014-01-01 00:00:00
abstract::Atherosclerotic plaque rupture may trigger the formation of mural thrombus. This thrombus formation is apparently affected by very high and complex shear conditions introduced by the luminal narrowing (stenosis) of the atheroma. To study the impact of such blood flow behaviour on thrombus formation we employed a model...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numb...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH17-06-0433
更新日期:2017-12-01 00:00:00
abstract::Fibrin sealant use in the United States has been limited because of the lack of a commercially available, government approved product. However, the significant need and usefulness of this material at the time of surgical operations has stimulated alternative sources of production. At the University of Virginia, the Bl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1995-07-01 00:00:00
abstract::Limited data are available on the role of monocytes in cardiac repair. In the present study, we evaluated the dynamic alterations of monocytes with reparative and angiogenic potential in patients with myocardial infarction(MI). Reparative CXCR4+ monocytes, and CD34+ and KDR+ monocytes with angiogenic potential derived...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-06-0395
更新日期:2013-02-01 00:00:00
abstract::The GAS6/ProS-TAM system is composed of two vitamin K-dependent ligands (GAS6 and protein S) and their three protein tyrosine kinase receptors TYRO3, AXL and MERTK, known as the TAM receptors. The system plays a prominent role in conditions of injury, inflammation and repair. In murine models of atherosclerotic plaque...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-10-0630
更新日期:2011-05-01 00:00:00
abstract::Endothelial dysfunction and increased platelet aggregation may be involved in the pathogenesis of normal tissue radiation toxicity. This study assessed clopidogrel, an inhibitor of ADP-induced platelet aggregation, as a modulator of intestinal radiation injury (radiation enteropathy). Rat small intestine was exposed t...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
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 health, haemostasis and angiogenesis are tightly regulated processes, but may become deregulated in cancer. Recent evidence suggests that platelet activation may link these processes as platelets can release angiogenic factors such as vascular endothelial growth factor (VEGF). Furthermore, inflammation has also bee...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-11-0679
更新日期:2004-07-01 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::Sixty nine patients were treated with local intra-arterial urokinase (37,500 U/CTA. hr-1) for recent severe ischemia of lower limbs: 27 (40%) ultimately required amputation. The difference of amputation rate between the groups with and without thrombolysis was not significant (33% v. 42%). A biological study in 6 pati...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-06-30 00:00:00
abstract::This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-10-22 00:00:00
abstract::Fibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly 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:1993-12-20 00:00:00
abstract::Post-infusion hepatitis is known to occur very frequently in haemophiliacs after treatment with unheated commercial clotting factor concentrates, obtained from large plasma donation pool. On the contrary, single-donor cryoprecipitate is likely to carry a lower risk of transmitting hepatitis. To evaluate this hypothesi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-12-15 00:00:00
abstract::The increase in nitric oxide (NO) production in lipopolysaccharide (LPS)-induced sepsis is thought to contribute to the development of shock. However, NO could also play an antithrombotic role. Little is known about the modulating effect of NO on the endothelial overexpression and production of tissue factor (TF) and ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-12-01 00:00:00
abstract::The cellular phospholipid, lysophosphatidic acid (LPA), released by activated platelets and fibroblasts or, at high levels, from ovarian and cervical carcinomas is a powerful serum mitogen that may modulate several signaling pathways in endothelial cells (EC). Hence, LPA could function in a paracrine manner during EC-...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::The aim of the present study was to analyse differences in the protein expression profile between platelets from aspirin (ASA)-resistant patients and ASA-sensitive patients. We analysed platelets from 51 clinically stable coronary ischaemic patients taking ASA (100 mg/day) divided into ASA-resistant (n=25) and ASA-sen...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-05-0290
更新日期:2010-01-01 00:00:00
abstract::A suggestive locus on chromosome 8 could be shown to be associated with familial high factor VIII (FVIII) levels in venous thromboembolism. The ADAMDEC 1 gene is a candidate expressing an ectodomain sheddase. However, the ectodomain of the clearance receptor for FVIII, the low-density lipoprotein receptor-related prot...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH08-01-0059
更新日期:2008-05-01 00:00:00
abstract::During treatment with vitamin K antagonists, International Normalized Ratios (INR) are determined periodically to maintain a therapeutic level of anticoagulation. We evaluated two existing methods for therapeutic quality control (linear interpolation and equidivision), with regard to their validity and reproducibility...
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:1999-10-01 00:00:00
abstract::A simple collagen binding assay (CBA) for measuring activity of the von Willebrand factor cleaving protease in clinical samples is described, and results of fifty masked plasmapheresis samples rom patients with TTP/HUS and other diseases are presented. There was 97.5% concordance between the CBA and a multimer gel ass...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::Coagulation factor XIII, a transglutaminase which stabilises blood clots by covalently cross-linking fibrin, is essential for normal haemostasis. FXIII deficiency results in a life-long bleeding disorder with added complications in wound healing and tissue repair. Sequence changes in the human FXIIIA gene, largely mis...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::Accumulation of the newly formed 14C-cyclic adenosine 3',5'-monophosphate (cyclic AMP) was found in the P1 (1.0) fraction, i.e. a platelet plasma membrane fraction which was obtained from 14C-adenine-labeled platelets. On the other hand, total cyclic AMP as determined simultaneously was located mainly in the platelet ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-02-28 00:00:00