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 plasma. In contrast to heparin, the sulfated galactan is still able to prolong coagulation time and delay thrombin and FXa generation in serpin-free plasma. We further investigated this effect using purified blood coagulation proteins, discovering that sulfated galactan inhibits the intrinsic tenase and prothrombinase complexes, which are critical for FXa and thrombin generation, respectively. We also investigated the mechanism by which sulfated galactan promotes FXa inhibition by antithrombin using specific recombinant mutants of the protease. We show that sulfated galactan interacts with the heparin-binding exosite of FXa and Arg-236 and Lys-240 of this site are critical residues for this interaction, as observed for heparin. Thus, sulfated galactan and heparin have similar high-affinity and specificity for interaction with FXa, though they have differences in their chemical structures. Similar to heparin, the ability of sulfated galactan to potentiate FXa inhibition by antithrombin is calcium-dependent. However, in contrast to heparin, this effect is not entirely dependent on the conformation of the gamma-carboxyglutamic acid-rich domain of the protease. In conclusion, sulfated galactan and heparin have some similar effects on blood coagulation, but also differ significantly at the molecular level. This sulfated galactan opens new perspective for the development of antithrombotic drugs.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Glauser BF,Rezende RM,Melo FR,Pereira MS,Francischetti IM,Monteiro RQ,Rezaie AR,Mourão PAdoi
10.1160/TH09-04-0273subject
Has Abstractpub_date
2009-12-01 00:00:00pages
1183-93issue
6eissn
0340-6245issn
2567-689Xpii
09-04-0273journal_volume
102pub_type
杂志文章abstract：:Vessel wall matrix changes occur after injury, although this has not been well studied in the venous system. This study tested the hypothesis that the thrombus dictates the vein wall response and vein wall damage is directly related to the duration of thrombus contact. To determine the injury response over time, rats ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-11-01 00:00:00
abstract：:Fibrinogen Matsumoto V (M-V) is a dysfibrinogen identified in a 52-year-old woman with systemic lupus erythematous. The triplet AGG encoding the amino acid residue Aalpha19 was replaced by GGG, resulting in the substitution of Arg-->Gly. Residue Aalpha19 has been shown to be one of the most important amino acids in th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Thirty-one individuals from 18 unrelated families with antithrombin deficiency have been identified as having a single point mutation within codon 384 (13268 GCA-->TCA) resulting in an alanine to serine substitution. Six families (11 individuals) were identified by the screening of individuals with thromboembolic dise...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:The antithrombotic effect of the thromboxane A2 receptor antagonist, vapiprost, was compared with those of other antiplatelet drugs using an arterial thrombosis model which utilized photochemical reaction in the rat femoral artery. Vapiprost prolonged the time required to occlude the artery with thrombus and inhibited...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-10-05 00:00:00
abstract：:The walls of rabbit mesenteric arterioles and venules (diameter 20 to 40 microns) were punctured with glass micropipets (tip diameter 6 to 8 microns). Thromboembolic reactions resulting from this standardized, small mechanical vessel wall injury could be quantified in vivo with the use of intravital video-microscopy. ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-02-25 00:00:00
abstract：:The aim was to investigate the perioperative risk of ischaemic and bleeding events in patients with coronary stents undergoing cardiac and non-cardiac surgery and how these outcomes are affected by the perioperative use of oral antiplatelet therapy. This was a multicentre, retrospective, observational study conducted ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH14-05-0436
更新日期：2015-02-01 00:00:00
abstract：:Antithrombin III (ATIII) deficiency is one of the few known abnormalities of the coagulation system known to predispose to venous thromboembolism but its relation to arterial disease is not established. We describe two related patients with this disorder, both of whom suffered arterial thrombotic events, at an early a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-02-19 00:00:00
abstract：:Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0038-1648251
更新日期：2018-06-01 00:00:00
abstract：:The major plasmin inhibitors namely alpha2-plasmin inhibitor and alpha2-macroglobulin were compared for their effects on lysis of fibrin clot. Plasmin fibrinolytic activity was immediately inhibited by alpha2-plasmin inhibitor, whereas alpha2-macroglobulin inhibited plasmin progressively. Urokinase(plasminogen activat...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-02-28 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
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH13-06-0484
更新日期：2014-03-03 00:00:00
abstract：:A new method to determine the concentration of free protein S in plasma is described. It is an enzyme-linked ligandsorbent assay (ELSA) which utilises the protein S binding capacity of the natural ligand C4b-binding protein (C4BP) to capture the free protein S from plasma samples. The use of C4BP as ligand in the assa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:The effect of shear rate and fibrinogen concentration on adenosine diphosphate-induced aggregation of suspensions of washed human platelets in Poiseuille flow at 23 degrees C was studied using a previously described double infusion technique and resistive particle counter size analysis. Using suspensions of multiple-c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:Various tests were evaluated for their capacity to differentiate between platelet suspensions with different degrees of cell damage. Those suspensions were prepared by simultaneous isolation of platelets from the same platelet-rich plasma (PRP) using the following procedures: 1. centrifugation at 4 degrees C with EDTA...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-02-28 00:00:00
abstract：:Although there is considerable evidence that platelet activation is associated with polymerization of actin, it is not known whether there is some pre-existing F-actin even before activation. We have examined the state of actin polymerization in nonactivated platelets by deoxyribonuclease assay of G-actin and total ac...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-10-29 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-11-24 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-11-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-08-04 00:00:00
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journal_title：Thrombosis and haemostasis
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-02-0106
更新日期：2005-01-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-10-28 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-10-0729
更新日期：2018-02-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-02-18 00:00:00
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
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-08-30 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
