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      Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation

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          Abstract

          The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B 2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl 3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl 3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow.

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          Most cited references18

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          THE AGGREGATION OF BLOOD PLATELETS.

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            Thrombus formation in vivo.

            To examine thrombus formation in a living mouse, new technologies involving intravital videomicroscopy have been applied to the analysis of vascular windows to directly visualize arterioles and venules. After vessel wall injury in the microcirculation, thrombus development can be imaged in real time. These systems have been used to explore the role of platelets, blood coagulation proteins, endothelium, and the vessel wall during thrombus formation. The study of biochemistry and cell biology in a living animal offers new understanding of physiology and pathology in complex biologic systems.
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              Signaling events underlying thrombus formation.

              Recent in vivo studies have highlighted the dynamic and complex nature of platelet thrombus growth and the requirement for multiple adhesive receptor-ligand interactions in this process. In particular, the importance of von Willebrand factor (VWF) in promoting both primary adhesion and aggregation under high shear conditions is now well established. In general, the efficiency with which platelets adhere and aggregate at sites of vessel wall injury is dependent on the synergistic action of various adhesive and soluble agonist receptors, with the contribution of each of the individual receptors dependent on the prevailing blood flow conditions. In this review, we will discuss the major platelet adhesive interactions regulating platelet thrombus formation under high shear, with specific focus on the VWF (GPIb and integrin alphaIIbbeta3) and collagen receptors (GPVI and integrin alpha2beta1). We will also discuss the signaling mechanisms utilized by these receptors to induce platelet activation with specific emphasis on the role of cytosolic calcium flux in regulating platelet adhesion dynamics. The role of soluble agonists in promoting thrombus growth will be highlighted and a model to explain the synergistic requirement for adhesive and soluble stimuli for efficient platelet aggregation will be discussed.
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                Author and article information

                Journal
                Lab Anim Res
                Lab Anim Res
                LAR
                Laboratory Animal Research
                Korean Association for Laboratory Animal Science
                1738-6055
                2233-7660
                December 2013
                20 December 2013
                : 29
                : 4
                : 221-225
                Affiliations
                [1 ]College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.
                [2 ]Misuba RTech Co., Ltd., Asan, Korea.
                [3 ]Daejeon Health Sciences College, Daejeon, Korea.
                [4 ]College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
                Author notes
                Corresponding author: Yun-Bae Kim, College of Veterinary Medicine, Chungbuk National University, 52 Naesudongro (Gaesin-dong), Cheongju, Chungbuk 361-763, Korea. Tel: +82-43-261-3358; Fax: +82-43-271-3246; solar93@ 123456cbu.ac.kr
                Corresponding author: Man Hee Rhee, College of Veterinary Medicine, Kyungpook National University, 80 Daehakro (Sangyeok-dong), Daegu 702-701, Korea. Tel: +82-53-950-5967; Fax: +82-53-950-5955; rheemh@ 123456knu.ac.kr

                #These two authors contributed equally to this work.

                Article
                10.5625/lar.2013.29.4.221
                3879341
                24396387
                fc8f1117-5800-471c-ae40-98dfcd88edfe
                Copyright © 2013 Korean Association for Laboratory Animal Science

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 November 2013
                : 22 November 2013
                : 26 November 2013
                Funding
                Funded by: National Research Foundation
                Award ID: 2009-0094034
                Categories
                Letter

                Life sciences
                platelet aggregation,thrombosis,nattokinase,thromboxane b2
                Life sciences
                platelet aggregation, thrombosis, nattokinase, thromboxane b2

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