Abstract：
:Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation to activated protein C (APC) by thrombin down-regulates the clotting cascade by limited proteolysis of the procoagulant cofactors Va and VIIIa. In addition to its anticoagulant activity, APC also exhibits potent cytoprotective and anti-inflammatory activities. While the anticoagulant activity of APC is enhanced by the cofactor function of protein S on membrane phospholipids, the cytoprotective intracellular signalling activity of APC requires complex formation with endothelial protein C receptor (EPCR) expressed on the vascular endothelium. Two natural variants of APC [Arg-147 to Trp substitution (R147W) and Lys-150 deletion (K150del)] have been identified in the Chinese population as hotspot mutants occurring with high frequencies of 27.8% and 13.9%, respectively, among 36 protein C-deficient subjects. The affected individuals exhibit variable thrombotic tendencies. To understand the underlying cause of the thrombotic phenotype in these patients, we expressed these two protein C variants in mammalian cells and characterised their anticoagulant and anti-inflammatory properties using established in vitro and cellular assays. Our results suggest that both R147W and K150del variants have normal amidolytic and proteolytic activities in the absence of cofactors. However, the R147W mutant exhibits ~3 times lower affinity for binding to EPCR and the K150del variant has ~2-3-fold impaired anticoagulant activity in the presence of protein S. These results provide some insight into the possible pathogenic mechanism of protein C deficiency in Chinese patients carrying these mutations.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Ding Q,Yang L,Hassanian SM,Rezaie ARdoi
10.1160/TH12-10-0760subject
Has Abstractpub_date
2013-04-01 00:00:00pages
614-24issue
4eissn
0340-6245issn
2567-689Xpii
12-10-0760journal_volume
109pub_type
杂志文章abstract：:alpha-Granule protein storage is important for producing platelets with normal haemostatic function. The low to undetectable levels of several megakaryocyte-synthesized alpha-granule proteins in normal plasma suggest megakaryocytes are important to sequester these proteins in vivo. alpha-Granule protein storage in vit...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-02-0125
更新日期：2003-11-01 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：:The prevalence of coagulation disorders in patients with upper extremity deep-vein thrombosis (UE-DVT) is unknown due to only a few observational studies of limited size reporting varying results. Therefore, we aimed to evaluate the prevalence of thrombophilia in patients with UE-DVT compared to patients with lower ex...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-09-01 00:00:00
abstract：:Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. How...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:We investigated the molecular basis of hypofibrinogenaemia in a woman with a history of recurrent, pregnancy-associated bleeding, and miscarriage. She had a Clauss fibrinogen of 0.9 mg/ml and SDS PAGE of purified fibrinogen showed a normal pattern of chains. However careful inspection of reverse phase chain separation...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：:Although sepsis-induced release of nitric oxide (NO) is known to have an antithrombotic effect, it is unknown if NO exerts this same effect under physiological conditions. We have there-fore attempted to determine whether or not NO protects against thrombus formation in normal Wistar rats injected with various amounts...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-05-0292
更新日期：2004-01-01 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：:The interdependence of the predictive accuracy of serum osteoprotegerin (OPG) and von Willebrand factor (vWF) levels for long-term cardiovascular outcomes has not been investigated so far. This was a prospective observational cohort study in 361 patients with coronary artery disease undergoing percutaneous coronary in...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-02-0087
更新日期：2017-08-30 00:00:00
abstract：:Catabolism of coagulation factor VIII (FVIII) is mediated by low-density lipoprotein receptor-related protein (LRP). The ligand-binding sites of LRP are formed by complement-type repeats (CR), and CR clusters II and IV bind most of LRP ligands. FVIII contains two major LRP-binding sites located in the A2 and A3 domain...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-12-01 00:00:00
abstract：:Thirty-one non-hemophilic patients with acquired antibodies to factor VIII were entered into a prospective, randomized, multi-institutional trial to determine the safety and efficacy of prednisone (P), cyclophosphamide (C), or the combination in the treatment of this disorder. Patients were eligible if they had antibo...
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：1993-11-15 00:00:00
abstract：:In patients with deep vein thrombosis (DVT), the factors which predispose to concomitant symptomatic pulmonary embolism (PE) have remained uncertain. From a prospective cohort of 5,451 consecutive patients with ultrasound-confirmed DVT, we analyzed 4,211 patients with a known status for presence (n=639) or absence (n=...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-09-0587
更新日期：2005-03-01 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：:Heparin and low-molecular-weight heparin (LMWH) are commonly monitored by determination of activated clotting times or chromogenic assays. Despite their wide use, these assays determine the biological activity and not the concentration of the anticoagulants. They may be inaccurate in some circumstances such as certain...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-03-0168
更新日期：2009-11-01 00:00:00
abstract：:Fibrinogen degradation products formed by the action of purified haemolymph and saliva of a Saturnidae caterpillar of the Lonomia genus were studies by immunoelectrophoresis and polyacrylamide/SDS gel electrophoresis. The pattern of degradation differ form the one described for plasmin, trypsin, brinase, and ochrase. ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1981-06-30 00:00:00
abstract：:An abnormal fibrinogen was discovered in the plasma of a clinically asymptomatic woman. This fibrinogen variant was analyzed by high resolution two-dimensional gel electrophoresis and its molecular abnormality established consisting in a slight decrease in molecular mass of the B beta-chains. Analysis of fibrin reveal...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-04-08 00:00:00
abstract：:Shear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with u...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-12-0854
更新日期：2010-09-01 00:00:00
abstract：:Risk scores in patients with atrial fibrillation (AF) based on clinical factors alone generally have only modest predictive value for predicting high risk patients that sustain events. Biomarkers might be an attractive prognostic tool to improve bleeding risk prediction. The new ABC-Bleeding score performed better tha...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-07-0478
更新日期：2017-10-05 00:00:00
abstract：:The multimeric plasma glycoprotein von Willebrand factor (VWF) is best known for recruiting platelets to sites of injury during primary hemostasis. Generally, mutations in the VWF gene lead to loss of hemostatic activity and thus the bleeding disorder von Willebrand Disease. By employing cone and platelet aggregometry...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/a-1344-4405
更新日期：2020-12-31 00:00:00
abstract：BACKGROUND: Cardiac-enriched micro ribonucleic acids (miRNAs) are released into the circulation following ST-elevation myocardial infarction (STEMI). Lack of standardized approaches for reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) data normalization and presence of RT-qPCR inhibitors...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0038-1660437
更新日期：2018-07-01 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：:Microparticles (MPs) are formed from platelets (PMPs), endothelial cells (EMPs) and monocytes (MMPs), and in acute myocardial infarction (MI), there is an increase of MPs in the culprit artery. In this study MPs were evaluated in whole blood in 105 patients with MI at five time-points during a two-year follow-up (FU)....
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-11-0837
更新日期：2017-07-26 00:00:00
abstract：:Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the bl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH03-12-0766
更新日期：2004-03-01 00:00:00
abstract：:This study was carried out in order to compare the coagulation balance in patients with colorectal cancer before and after surgical removal of tumor with an age matched non-malignancy control group. Furthermore, it was studied whether preoperative coagulation state in cancer patients was correlated to the postoperativ...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Several studies have highlighted a specific role for membrane cholesterol domains in platelet signalling. Upon adhesion to von Willebrand factor (VWF) or collagen, cholesterol-rich domains (CRDs) accumulate in filopodial extensions and selectively harbour counterpart receptors (GPIb and GPVI) and associated signalling...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH07-08-0528
更新日期：2008-06-01 00:00:00
abstract：:Angiogenic activity and formation of a vascular network facilitate tumor perfusion and play a critical role in tumor growth and metastasis. Tumor vasculature may be visualized by means of parametric imaging of specific morphological and physiological characteristics that collectively describe its properties. In this r...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2003-01-01 00:00:00
abstract：:The terms glycoprotein IV (GPIV) and glycoprotein IIIb (GPIIIb) have been used interchangeably and reports in the literature have indicated this glycoprotein as having a molecular weight variously described as either 88,000 or 97,000, a fast anodal mobility on crossed electrophoresis and either 13 or less than 1 methi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-02-19 00:00:00
abstract：:The efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well-documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combi...
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：1997-05-01 00:00:00
abstract：:Injection of human alpha 2-antiplasmin resulted in delayed elimination of fibrin from the lungs in rats with thrombin-induced intravascular coagulation. The amount of alpha 2-antiplasmin injected was chosen so as to simulate the posttraumatic increase of this inhibitor in man. By injecting trace amounts only of radiol...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1981-12-23 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：:Causative mutations in the factor VIII gene of seven unrelated patients with severe haemophilia A were identified using the mutation screening procedure conformation sensitive gel electrophoresis (1) and characterised by direct sequencing. Female family members of all patients had requested either carrier status deter...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
