• Title/Summary/Keyword: Coagulation cascade

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Purification and Characterization of Anticoagulant Protein from Ark Shell, Scapharca broughtonii

  • Jung, Won-Kyo;Park, Pyo-Jam;Kim, Se-Kwon
    • Proceedings of the Korean Society of Fisheries Technology Conference
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    • 2000.05a
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    • pp.90-91
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    • 2000
  • The physiological systems that control blood fluidity are both complex and elegant. Blood must remain fluid within the vasculature and yet clot quickly when exposed to nonendothelial surfaces at sites of vascular injury. There are two principle mechanisms to control a delicate balance in higher organisms (Davie & Ratnoff, 1964). Present evidence suggests that the intrinsic pathway play an important role in the growth and maintenance of fibrin formation in the coagulation cascade while a second overlapping mechanism, called the extrinsic pathway, is critical in the initiation of fibrin formation. Coagulation factors is in two mechanisms, and in order to clot blood, they are activated by a cooperation with $Ca^{2+}$, phospholipid and vitamin K etc. For example, the human placental anticoagulant protein (PAP of PAP- I), which is a $Ca^{2+}$ -dependent phospholipid binding protein (Funakoshi et al., 1987) inhibited the activity of factor Xa, so that it prolonged fibrin formation. We wondered whether any other protein was involved in regulation of the coagulant system as an anticoagulant protein from natural organisms. Natural agents would have not harmful side-effects in comparision with chemically synthesized materials such as warfarin, aspirin, phenindione, etc.. But anticoagulant agents from natural, especially marine organisms have hardly been researched except for polysaccharides from marine algae. (omitted)

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Panax ginseng: Inflammation, platelet aggregation, thrombus formation, and atherosclerosis crosstalk

  • Lee, Yuan Yee;Kim, Sung Dae;Park, Seung-Chun;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.46 no.1
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    • pp.54-61
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    • 2022
  • Ginseng has been widely studied due to its various therapeutic properties on various diseases such as cardiovascular disease (CVD). Cardiovascular disease has been canonically known to be caused by high levels of low-density lipoproteins (LDL) in the bloodstream, in addition to the impaired vasodilatory effects of cholesterol. However, current research on CVD has revealed a cascade of mechanisms involving a series of events that contribute to the progression of CVD. Although this has been elucidated and summarized in previous studies the detailed correlation between platelet aggregation and innate immunity that plays an important role in CVD progression has not been thoroughly summarized. Furthermore, immune cell subtypes also contribute to the progression of plaque formation in the subendothelial layer. Thrombus formation and the coagulation cascade also have a vital role in the progression of atherosclerosis. Hence, in this mini review we aim to elucidate, summarize, and propose the potent therapeutic effect of ginseng on CVD, mainly on platelet aggregation, plaque formation, and thrombus formation.

Anticoagulant Activity of Sulfated Polysaccharides Isolated from Codium fragile (청각 산추출물에서 정제한 함황다당류의 항응고활성)

  • Park, Mee-Kyung;Kweon, Mee-Hyang;Cho, Hong-Yon;Yang, Han-Chul
    • Applied Biological Chemistry
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    • v.42 no.2
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    • pp.140-146
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    • 1999
  • We have isolated two anticoagulant polysaccharides from an acidic extract of Codium fragile. The purification was conducted using three consecutive chromatographies of DEAE-Toyopearl 650C, Sephadex G-100 (G-75), and Sepharose CL-6B by measuring activated partial thromboplastin time (APTT). The two purified anticoagulant polysaccharides, CF-1-VIa-1 and CF-1-VIIa-1, were found to be nearly homogenous on HPLC using a gel permeation column and appeared to have molecular weights of about 80,000 Da and 40,000 Da, respectively. The polysaccharides consisted mainly of arabinose and galactose in a molar ratio of about 2 : 1, and also comprised 12-13% of sulfates at their constituent sugars. CF-1-VIa-1 and CF-1-VIIa-1 inhibited blood coagulation via both the intrinsic and the extrinsic pathways. The polysaccharides unlike heparin showed an inhibitory activity on thrombin when a pure fibrinogen without antithrombin III was used as a substrate. Structural modifications using sulfation and desulfation affected the anticoagulant activities directly, suggesting that the content of sulfate plays an important role in the blood coagulation cascade. The polysaccharides may inhibit some proteases involved in the blood coagulation cascade, judging from the independence of calcium concentrations in their anticoagulant activity.

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Evaluation of Biomolecular Interactions of Sulfated Polysaccharide Isolated from Grateloupia filicina on Blood Coagulation Factors

  • Athukorala, Yasantha;Jung, Won-Kyo;Park, Pyo-Jam;Lee, Young-Jae;Kim, Se-Kwon;Vasanthan, Thava;No, Hong-Kyoon;Jeon, You-Jin
    • Journal of Microbiology and Biotechnology
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    • v.18 no.3
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    • pp.503-511
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    • 2008
  • An edible marine red alga, Grateloupia filicina, collected from Jeju Island of Korea was hydrolyzed by cheap food-grade carbohydrases (Viscozyme, Celuclast, AMC, Termamyl, and Ultraflo) to investigate its anticoagulant activity. Among the tested enzymatic extracts of G. filicina, a Termamyl extract showed the highest anticoagulant activity. Anion-exchange chromatography on DEAE-cellulose and gel-permeation chromatography on Sepharose-4B were used to purify the active polysaccharide from the crude polysaccharide fraction of G. filicina. The purified sulfated polysaccharide (0.42 sulfate/total sugar) showed ${\sim}1,357kDa$ molecular mass and was comprised mainly of galactose(98%) and 1-2% of glucose. The sample showed potential anticoagulant activity on activated partial thromboplastin time (APTT) thrombin time (TT) assays. The purified G. filicina anticoagulant (GFA) inhibited the coagulation factor X (92%), factor II (82%), and factor VII (68%) of the coagulation cascade, and the molecular interaction (protein-polysaccharide) was highly enhanced in the presence of ATIII (antithrombin III). The dissociation constant of polysaccharide towards serine proteins decreased in the order of FXa (58.9 nM) >FIIa (74.6 nM) >FVII (109.3 nM). The low/less cytotoxicity of the polysaccharide benefits its use in the pharmaceutical industry; however, further studies that would help us to elucidate the mechanism of its activity are needed.

Antithrombotic Effect and Antiplatelet Activity of Polygonum cuspidatum Extract (호장근 추출물의 항혈전 효능 및 혈소판 응집 억제작용)

  • Yang, Won-Kyung;Sung, Yoon-Young;Kim, Ho-Kyoung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.2
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    • pp.168-173
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    • 2012
  • We performed this study to develop antithrombotic agents from oriental medicine herb extracts. Polygonum cuspidatum has been traditionally used as an edible medical resources for the treatment of cancer, pyodermatitis, hepatitis, cystitis, and inflammation. However, the effects of Polygonum cuspidatum on thrombosis and platelet activation are not precisely understood. The antithrombotic and antiplatelet activities of Polygonum cuspidatum were investigated by assessing the effect of a 70% ethanol extract of Polygonum cuspidatum on blood coagulation, fibrinolysis, and platelet aggregation. Polygonum cuspidatum showed effective fibrinolytic activity at 10 mg/mL. Polygonum cuspidatum also inhibited adenosine diphosphate induced platelet aggregation. Furthermore, evaluation of anticoagulant activity showed that an extract of Polygonum cuspidatum prolonged coagulation time via activated partial thromboplastin time (APTT). Our results show that Polygonum cuspidatum can be a potential candidate for antiplatelet activity as well as a fibrinolytic agent.

Serum proteomics analysis of feline mammary carcinoma based on label-free and PRM techniques

  • Zheng, Jia-San;Wei, Ren-Yue;Wang, Zheng;Zhu, Ting-Ting;Ruan, Hong-Ri;Wei, Xue;Hou, Kai-Wen;Wu, Rui
    • Journal of Veterinary Science
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    • v.21 no.3
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    • pp.45.1-45.15
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    • 2020
  • Background: Feline mammary carcinoma is the third most common cancer that affects female cats. Objectives: The purpose of this study was to screen differential serum proteins in feline and clarify the relationship between them and the occurrence of feline mammary carcinoma. Methods: Chinese pastoral cats were used as experimental animals. Six serum samples from cats with mammary carcinoma (group T) and six serum samples from healthy cats (group C) were selected. Differential protein analysis was performed using a Label-free technique, while parallel reaction monitoring (PRM) was performed to verify the screened differential proteins. Results: A total of 82 differential proteins were detected between group T and group C, of which 55 proteins were down regulated and 27 proteins were up regulated. Apolipoprotein A-I, Apolipoprotein A-II (ApoA-II), Apolipoprotein B (ApoB), Apolipoprotein C-III (ApoC-III), coagulation factor V, coagulation factor X, C1q, albumen (ALB) were all associated with the occurrence of feline mammary carcinoma. Differential proteins were involved in a total of 40 signaling pathways, among which the metabolic pathways associated with feline mammary carcinoma were the complement and coagulation cascade and cholesterol metabolism. According to the Label-free results, ApoB, ApoC-III, ApoA-II, FN1, an uncharacterized protein, and ALB were selected for PRM target verification. The results were consistent with the trend of the label-free. Conclusions: This experimen is the first to confirm ApoA-II and ApoB maybe new feline mammary carcinoma biomarkers and to analyze their mechanisms in the development of such carcinoma in feline.

New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism

  • Kim, Joo Hee;Lim, Kyung-Min;Gwak, Hye Sun
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.461-470
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    • 2017
  • Anticoagulant drugs, like vitamin K antagonists and heparin, have been the mainstay for the treatment and prevention of venous thromboembolic disease for many years. Although effective if appropriately used, traditional anticoagulants have several limitations such as unpredictable pharmacologic and pharmacokinetic responses and various adverse effects including serious bleeding complications. New oral anticoagulants have recently emerged as an alternative because of their rapid onset/offset of action, predictable linear dose-response relationships and fewer drug interactions. However, they are still associated with problems such as bleeding, lack of reversal agents and standard laboratory monitoring. In an attempt to overcome these drawbacks, key steps of the hemostatic pathway are investigated as targets for anticoagulation. Here we reviewed the traditional and new anticoagulants with respect to their targets in the coagulation cascade, along with their therapeutic advantages and disadvantages. In addition, investigational anticoagulant drugs currently in the development stages were introduced.

Blood Compatibility of Hollow Fiber Membranes Treated with Plasma Polymerization (플라즈마 중합 처리된 중공사 막의 혈액 적합성)

  • Kwon O. S.;Lee S. C.
    • Korean Journal of Materials Research
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    • v.15 no.8
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    • pp.521-527
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    • 2005
  • Surface modification of polypropylene hollow fiber membranes was peformed in order to develop blood-compatible biomaterials for use in the blood contacting and oxygenation membranes of a lung-assist device(LAD). Blood compatibility was determined by using anticoagulation blood and evaluating formation of blood clots on their surfaces as well as activation of plasma coagulation cascade, platelet adhesion, and aggregation. It was verified that the number of platelets on the silicone coated fibers was significantly lower than those on polypropylene. It was also found that the polypropylene hollow fiber membranes using plasma treatment exhibited suppression of complement activation in blood compatibility test.

A Novel Anticoagulant Protein from Scapharca broughtonii

  • Jung, Won-Kyo;Je, Jae-Young;Kim, Hee-Ju;Kim, Se-Kwon
    • BMB Reports
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    • v.35 no.2
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    • pp.199-205
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    • 2002
  • An anticoagulant protein was purified from the edible portion of a blood ark shell, Scapharca broughtonii, by ammonium sulfate precipitation and column chromatography on DEAE-Sephadex A-50, Sephadex G-75, DEAE-Sephacel, and Biogel P-l00. In vitro assays with human plasma, the anticoagulant from 'S. broughtonii, prolonged the activated partial thromboplastin time (APTT) and inhibited the factor LX in the intrinsic pathway of the blood coagulation cascade. But, the fibrin plate assay did not show that the anticoagulant is a fibrinolytic protease. The molecular mass of the purified S. broughtonii anticoagulant was measured to be about 26.0kDa by gel filtration on a Sephadex G-75 column and SDS-PAGE under denaturing conditions. The optimum activity in the APTT assay was exhibited at pH 7.0-7.5 and $40-45^{\circ}C$ in the presence of $Ca^{2+}$.

Antiplatelet and antithrombotic activities of purpurogallin in vitro and in vivo

  • Ku, Sae-Kwang;Bae, Jong-Sup
    • BMB Reports
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    • v.47 no.7
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    • pp.376-381
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    • 2014
  • Enzymatic oxidation of pyrogallol was efficiently transformed to an oxidative product, purpurogallin (PPG). Here, the anticoagulant activities of PPG were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin and activated factor X (FXa). And, the effects of PPG on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated in tumor necrosis factor (TNF)-${\alpha}$ activated human umbilical vein endothelial cells (HUVECs). Treatment with PPG resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, as well as inhibited production of thrombin and FXa in HUVECs. In addition, PPG inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. PPG also elicited anticoagulant effects in mice. In addition, treatment with PPG resulted in significant reduction of the PAI-1 to t-PA ratio. Collectively, PPG possesses antithrombotic activities and offers a basis for development of a novel anticoagulant.