Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity.
ABSTRACT The vegetable cheese-like food, natto, is extremely popular in Japan with a history extending back over 1000 years. A fibrinolytic enzyme, termed nattokinase, can be extracted from natto; the enzyme is a subtilisin-like serine protease composed of 275 amino acid residues and has a molecular weight of 27.7 kDa. In vitro and in vivo studies have consistently demonstrated the potent pro-fibrinolytic effect of the enzyme. However, no studies to date have evaluated the effects of nattokinase on various hemorheological parameters and thus we have begun to assess the effects of the enzyme on RBC aggregation and blood viscosity. Blood samples were incubated with nattokinase (final activities of 0, 15.6, 31.3, 62.5 and 125 units/ml) for 30 minutes at 37 degrees C. RBC aggregation was measured using a Myrenne MA-1 aggregometer and blood viscosity assessed over 1-1000 s(-1) with a computer controlled scanning capillary rheometer (Rheolog). Our in vitro results showed a significant, dose-dependent decrease of RBC aggregation and low-shear viscosity, with these beneficial effects evident at concentrations similar to those achieved in previous in vivo animal trials. Our preliminary data thus indicate positive in vitro hemorheological effects of nattokinase, and suggest its potential value as a therapeutic agent and the need for additional studies and clinical trials.
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ABSTRACT: Nattokinase is a potent fibrinolytic enzyme, obtained from 'natto' a traditional food in Japan. It breaks fibrin strands both by hydrolyzing fibrin in blood clots directly and hastens the production of tissue plasminogen Activator. It was also found to be lower the blood pressure and has been used in the management of atherosclerosis, coronary artery disease, and stroke. Endothelin-1 (ET-1) is a very potent vasoconstrictor and binds to smooth muscle endothelin receptor. ET-1 has been shown to be released by the failing myocardium where it can contribute to cardiac calcium overload and hypertrophy. In this study we conducted studies to evaluate the cardiac rate and some biochemical parameters to ascertain the interaction between endothelin antagonist BQ-123 and nattokinase. INTRODUCTION Nattokinase was first found and extracted from 'natto', which is a boiled and fermented soyabean a traditional food in Japan (Maruyama and Sumi, 1995 and Sumi et al., 1987). Nattokinase is a potent fibrinolytic enzyme that effectively breaks down fibrin strands and thrombi. Nattokinase can both hydrolyze fibrin in blood clots directly and hasten the production of t-PA (Tissue Plasminogen Activator), which activates plasminogen into active plasmin to hydrolyze fibrin (Sumi et al., 1990). Decreasing blood viscosity strikes at the root of arteriosclerosis and atherosclerosis as well as hypertension, peripheral vascular disease and congestive heart failure 1 . The fibrinolytic activity of nattokinase resolves the active process of atherosclerosis and lyses the thrombi. The per oral administration along with prolonged half-life of 4-6 hours and extremely safe profile show favourably upon nattokinase as the key agent for restoration of vasculature health (Sumi et al., 1990 and Kim et al., 2008).While on the other hand the vasoconstrictor peptide, Endothelin-1 (ET-1) is a 21 amino acid peptide that is produced by the vascular endothelium. It is a very potent vasoconstrictor that binds to smooth muscle endothelin receptors, of which there are two subtypes: ETA and ETB receptors (Schiffrin and Touyz, 1998). These receptors are coupled to a Gq-protein and receptor activation leads to the formation of IP3, which induces the release of calcium by the sarcoplasmic reticulum (SR) and increased smooth muscle contraction and vasoconstriction. An increase in endothelin may cause altered cardiovascular hemodynamics (Gulati et al., 1996). There are also ETB receptors located on the endothelium that stimulate the formation of nitric oxide, which produces vasodilation in the absence of smooth muscle ETA and ETB receptor activation. This receptor distribution helps to explain the phenomenon that ET-1 administration causes transient vasodilation (initial endothelial ETB activation) and hypotension, followed by prolong vasoconstriction (smooth muscle ETA and ETB activation) and hypertension. ET-1 receptors in the heart are also linked to the Gq protein and IP3 signal transduction pathway. Therefore, ET-1 in the heart causes SR release of calcium, which increases contractility. ET-1 also increases the heart rate (Bascon et al., 1996). Endothelin receptor antagonists, by blocking the vasoconstrictor and cardiotonic effects of ET-1, produce vasodilation and cardiac inhibition. Endothelin receptor antagonists have been shown to decrease mortality and improve hemodynamic in experimental models of heart failure (Barker et al., 2001). Congestive heart failure is a disease process characterized by impaired left ventricular function, increased peripheral and pulmonary vascular resistance and sodium and water retention. Since the prevalence ofInternational Journal of Basic and Applied Medical Sciences. 11/2013; ISSN:2277-2103.
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ABSTRACT: Elevated blood viscosity is a risk factor for atherosclerosis, thrombosis and other cardiovascular events. Our previous studies have suggested that consumption of Yerba mate tea (Ilex paraguariensis) has strong antioxidant and lipid-lowering properties in animals. The in vivo effects of Yerba mate on blood viscosity in humans, however, have not been studied. This study aims to investigate the effect of Yerba mate tea on the reduction of blood viscosity and the improvement of microcirculatory parameters commonly regarded as risk factors for serious cardio and cerebrovascular disorders. 142 subjects with high blood viscosity were recruited in this randomized, double-blind, placebo-controlled study. Yerba mate tea or placebo (5g/day) was administered to different groups for 6weeks. After treatment, results of hemorheological indexes, nailfold microcirculation, 6-keto-PGF1α and TXB2 and lipid profiles of subjects in the Yerba mate tea group were compared with those in the placebo-receiving group. Parameters of blood viscosity and microcirculation were improved in the subjects from the Yerba mate tea group but not in placebo-receiving patients. After treatment, whole blood viscosity, plasma viscosity and the Equation K value of erythrocyte sedimentation rate (ESRK) decreased significantly in the Yerba mate group. Meanwhile, shape, flow state and nailfold microcirculation appeared positively changed. Specifically, blood flow speeds accelerated gradually and nailfold weighted integral values decreased significantly. Moreover, the vasodilator 6-keto PGF1α increased while the thromboxane TXB2 decreased in serum samples of subjects in the Yerba mate-receiving group. Overall, Yerba mate tea-receiving subjects saw nearly all measured values improve to levels comparable to those characteristic of patients with normal microcirculation. These results indicate the therapeutic capacity of Yerba mate tea in the treatment of high blood viscosity. Here, Yerba mate tea played a role in the regulation of various indexes of hemorheology, nailfold microcirculation, and the platelet aggregating factors 6-keto-PGF1a and TXB2. The regulation of these might be correlated with reduced blood viscosity and accelerating blood flow. Thus, Yerba mate tea may reduce some key risk-factors of cardiovascular disease. Daily consumption of Yerba mate tea may be a better-tolerated option for individuals with high blood viscosity and microcirculatory disturbance and as such, a novel preventative strategy for patients at-risk for vascular disease. Copyright © 2014. Published by Elsevier Inc.Experimental Gerontology 01/2015; · 3.53 Impact Factor
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ABSTRACT: The difficulty of diagnosing blood clots makes salient the question, "What role does family history awareness have for guiding lay and expert actions?" The authors examine the in-depth life reflection interviews of 20 women who experienced a first venous blood clot between the ages of 18 and 50 years, identifying causal attributions the women made for thrombosis after the event. Twelve participants described an understanding of the cascade of events linked to thrombosis, revealing that there is seldom a single cause. The other eight identified belief in a single determining cause for their thrombosis. The authors reflect on the symptoms the women experienced during the course of the clotting event, patterns of care that they executed to self-manage their blood clot, and their misdiagnoses associated with symptoms and care. The women recalled the patterns of care received through formal health care systems and the reported misdiagnoses linked to these interactions. The recollections reveal that the subtle nature of venous blood clot symptoms contributes to lay and expert misdiagnoses. Use of antibiotics and pain killers in the wake of misdiagnosis masks symptoms, contributing to costly delays in accurate diagnoses. Four women were aware of a family history of clotting when the event occurred, 13 had such a history but lacked awareness until the clotting event, and three had no known history. Among women with awareness of their family history, blood clot diagnosis occurred sooner, promoting survival and efficiencies in health care. Implications for communicating about family history of thrombosis are considered.Journal of Health Communication 05/2014; 20(1):1-14. · 1.61 Impact Factor