Abstract:
:The effect of a basic synthetic peptide, representing the C-terminal region of tissue factor pathway inhibitor (TFPI - Lys254 - Met276), as well as that of the whole protein, on the activity of lipoprotein lipase (LPL) is described. The activity of bovine LPL was measured by chromogenic assay using a water-soluble chromogenic substrate, p-nitrophenyl butyrate. Five and 10 microM concentrations of the peptide increased Vmax of bovine LPL by 48.9% and 85.6% respectively as compared with the buffer control without affecting Km. Poly l-lysine, though positively charged did not have any effect, suggesting the importance of the amino acid sequence of the test peptide. On the other hand, 0.25, 0.5 and 1.0 mM n-butyric acid - a product of LPL catalysis in the chromogenic assay, when added to the incubation mixture decreased Vmax non competitively by 22.8%, 40.4% and 63% respectively as compared with buffer control, confirming the known product inhibition of LPL. A 100-fold molar excess of n-butyric acid produced inhibition of the LPL reaction as compared with the synthetic peptide which produced potentiation, suggesting a 1:100 stoichiometric interaction of the peptide with n-butyric acid. At a fixed concentration of 0.25 mM substrate, 10 nM full length recombinant TFPI, containing the basic C-terminal domain, increased velocity of LPL reaction by 39.4% as compared with buffer control. The same concentration of two-domain recombinant TFPI (TFPI1-160) had no effect. It is possible that negatively charged n-butyric acid is sequestered by the positively charged peptide or the basic region of recombinant full length TFPI. Relieving of product inhibition could then be a possible mechanism of the observed potentiation of bovine LPL activity by the basic peptide or full length recombinant TFPI. The 39.4% increase in reaction velocity of LPL catalysis produced by 10 nM full length recombinant TFPI was comparable to 38.9% increase produced by 5 microM of the basic peptide under the same conditions. A further increase of 78.7% was brought about by 10 microM concentration of the same peptide. The reason for about 500-fold increase in the potency of the whole protein as compared with that of the peptide is not clear. It is possible that in its tertiary conformational state, the whole protein is able to sequester product and relieve product inhibition more effectively than the short linear peptide. Rabbit polyclonal antiserum against the basic peptide partially inhibited LPL activity of human post heparin plasma, measured by radioenzymatic assay using triolein substrate. Since post heparin plasma contains full length TFPI, binding of the added antibody to its basic C-terminus and hence the relative unavailability of latter for product sequestration (oleic acid in this case) could explain the observed inhibition of human LPL activity by antibody against the peptide. Thus by enhancing lipase activity, full length TFPI may facilitate hydrolysis of triglyceride and concomitantly lower factor VII coagulant activity as demonstrated earlier, particularly after heparin injection when both TFPI and LPL are released in circulation.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Mukherjee M,Kakkar VVkeywords:
subject
Has Abstractpub_date
1999-12-01 00:00:00pages
1648-51issue
6eissn
0340-6245issn
2567-689Xpii
99121648journal_volume
82pub_type
杂志文章abstract::The prothrombin time (PT) test is used to monitor oral anticoagulant therapy. Contact activation of patient blood samples in vitro may shorten the PT and thus lead to underestimation of the degree of anticoagulation. Commercial evacuated tubes for blood collection have been reported to induce shortening of the PT. The...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-10-31 00:00:00
abstract::Individuals with lupus anticoagulants (LA) are at risk for thromboembolism (TE). Chronic inflammation is an important characteristic in LA patients which may dispose for TE. Platelets play a key role in inflammation and TE. We therefore investigated gene polymorphisms as well as plasma levels of platelet receptors as ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-04-01 00:00:00
abstract::Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysf...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-12-0831
更新日期:2005-09-01 00:00:00
abstract::Human fibrinogen was subjected to limited proteolytic attack by thrombin, batroxobin or Agkistrodon contortrix thrombin-like enzyme, yielding desAB-, desA- or desB-fibrin monomers, respectively. Turbidity curves demonstrated that, with all three enzymes, the polymerization process was strongly accelerated by increasin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-04-30 00:00:00
abstract::In high-risk and complicated coronary intervention, the risk of acute closure is unpredictable. Thrombus and platelet deposition at the intervention site may also have further effects on subsequent restenosis. In vivo infusion of activated protein C has previously been shown to achieve potent anticoagulation without a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::We performed experiments to determine whether endothelial cells synthesize phospholipid metabolites via the lipoxygenase pathway and whether these metabolites influence platelet/vessel wall interactions. Monolayers of cultured human endothelial cells were incubated with 14C-arachidonic acid and their cyclo-oxygenase a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-06-24 00:00:00
abstract::This review collects evidence about immune and inflammatory functions of platelets from a clinician's point of view. A focus on clinically relevant immune functions aims at stimulating further research, because the complexity of platelet immunity is incompletely understood and not yet translated into patient care. Pla...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-02-0146
更新日期:2014-10-01 00:00:00
abstract::Megakaryocyte (MK)-derived miRNAs have been detected in platelets. Here, we analysed the expression of platelet and circulating miR-223, miR-26b, miR-126 and miR-140 that might be altered with their target mRNAs in type 2 diabetes mellitus (DM2). MiRNAs were isolated from leukocyte-depleted platelets and plasma sample...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-04-0322
更新日期:2017-02-28 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::Cysteinyl leukotrienes (i.e. LTC4, LTD4), produced by activated leukocytes or by transcellular metabolism may act at different levels on vascular smooth muscle cells (VSMC) during inflammatory process or atherosclerosis. We studied the effect of LTC4, LTD4, and LTE4 on the in vitro proliferation of rat VSMC, measured ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions. The threshold concentration (TC) of ADR induc...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-10-31 00:00:00
abstract::The fibrin-specificity and procoagulant effects of recombinant staphylokinase (Sak42D) were compared with those of recombinant tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction. Plasma samples were obtained at baseline and at 25 and 90 min, from 24 patients who were randomly assign...
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:1996-12-01 00:00:00
abstract::A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 pat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-06-30 00:00:00
abstract::During the collection of samples for plasma beta-thromboglobulin (beta-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single beta-TG measurement, blood samples were collected simultaneously from both arms on two separate...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-04-07 00:00:00
abstract::Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To a...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1160/TH03-07-0457
更新日期:2003-09-01 00:00:00
abstract::The incidence of newly diagnosed malignancy is increased in patients with unexplained venous thromboembolism during the first year after a thromboembolic event in comparison to controls (odds ratio, 3.9-36). Extensive screening with computed tomography, endoscopy and tumor markers can identify most of these undetected...
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::Platelets are critically involved in atherosclerosis and acute thrombosis. The platelet phenotype shows a wide variability documented by the inherited difference of platelet reactivity, platelet volume and count and function of platelet surface receptors. Several candidate genes have been put into focus and investigat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH13-02-0145
更新日期:2013-11-01 00:00:00
abstract::Venous thromboembolism (VTE) is a multifactorial disease. Major provoking factors (e. g. surgery, cancer, major trauma, and immobilisation) are identified in 50-60 % of patients, while the remaining cases are classified as unprovoked. However, minor predisposing conditions may be detectable in these patients, possibly...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-06-0563
更新日期:2015-06-01 00:00:00
abstract:: ...
journal_title:Thrombosis and haemostasis
pub_type: 社论
doi:10.1055/s-0038-1676073
更新日期:2018-12-01 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::Mechanisms mediating initial adsorption of coagulation proteins to live cells were investigated. Adsorption kinetics were examined under varying flow conditions using tracer-dilution techniques in perfused spherical monolayers of cells expressing tissue factor. At biologically relevant time and concentration ranges, r...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::The aim of the present study was to evaluate the relative performance of five screening methods for APC resistance caused by the factor V:Q506 mutation: the original method Coatest APC Resistance Chromogenix, a modified method using the same reagents but a predilution 1+4 of the plasma in a factor V deficient plasma f...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::ADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and AD...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-11-0683
更新日期:2004-12-01 00:00:00
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...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH10-03-0195
更新日期:2010-11-01 00:00:00
abstract::Asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and paraoxonase 1 (PON1) are directly involved in the pathogenesis of atherosclerosis by modulation of oxidative stress and/or NO bioavailability. We aimed to assess whether endurance exercise which is known to be cardioprotective could beneficially affect thes...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-03-0158
更新日期:2005-12-01 00:00:00
abstract::We have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effects of uremic medium on the morphology of endothelial cells (ECs), and their resistance to flow was analyzed. The influence of uremic media on the reactivity of the extracellular matrix (ECM...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::Five expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; x3), Biostate (x3) and Humate/Haemate (x3). All laborato...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::We determined factor VII antigen (FVIIag) levels in 705 healthy blood donors ranging in age from 17 to 79 years using a two-site solid-phase enzyme immunoassay developed in our laboratory. The mean (+/- SD) FVIIag level for the total population was 102 +/- 31%. FVIIag levels for men (n = 375) and women (n = 330) were ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 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