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Atherothrombosis can be regarded as a 'life-style related disease' of which diet is one of the important risk factors. The prophylactic effect of partially defatted flaxseed meal (PDFM) on atherothrombosis has not yet been studied. The aim of this study was to assess the effect of PDFM and a lignan from flaxseed, secoisolariciresinol diglucoside (SDG), on thrombosis and atherogenesis. An earlier developed test, the quantitative assessment of laser-induced thrombus formation in the carotid artery of apolipoprotein E and low-density lipoprotein receptor deficient mice was used in this study. Thrombotic and atherosclerotic status was assessed in mice kept on a high-fat diet for 8 weeks (40% in energy). The diet contained 0.05% cholesterol alone (control) or the same cholesterol with added PDFM (5% w/w; 8.3 g/kg body weight per day) or SDG (0.06% w/w; 100 mg/kg body weight per day). PDFM showed antithrombotic (P < 0.01) and anti-atherogenic effect (P < 0.01). SDG did not affect either atherogenesis or thrombosis. This study suggests that dietary intake of PDFM can be beneficial in reducing the risk of high-fat-induced atherothrombosis.

In vitro and in vivo experimental models have demonstrated that vascular endothelial function is significantly impaired as a result of oxidative stress, mediated by the generation of oxygen-derived free radicals in response to chronic or acute inflammation. In particular, super-oxide () at specific concentrations leads to the impairment of nitric oxide (NO) bioactivity, and it is known that NO plays a fundamental role in the maintenance of vascular homeostasis. The relationship between reactive oxygen species (ROS) and NO release in thrombosis-related endothelial damage in the peripheral microvasculature remains unclear, however. The purpose of the present study was to investigate the effect of the free-radical scavenger, edaravone, on NO synthesis and thrombotic potential in arterioles after exposure to laser irradiation. Highly sensitive electrochemical NO microsensors were positioned in femoral arterioles of mice, and the kinetics of NO release were recorded in response to standardized laser irradiation in vivo. In addition, images of NO release from damaged vascular cells were investigated in a similar rat model using the NO-sensitive dye 4,5-diaminofluorescein diacetate (DAF-2DA). Thrombogenesis was assessed in carotid arterioles by continuous video microscopy using image analysis software. Laser irradiation led to NO release from perturbed endothelial cells and from platelet-rich thrombi. Edaravone had no significant effect on NO release in non-laser treated, intact endothelium compared with placebo. In contrast, edaravone demonstrated a dose-dependent effect on NO release and thrombogenicity. At a concentration of 10.5 mg/kg per h, edaravone promoted a 5-fold increase in NO and a reduction in platelet-rich thrombus volume to 58% of the placebo values. Our data provide direct evidence to confirm that acute endothelial damage in peripheral microvessels initially induces NO release and that the free-radical scavenger, edaravone, augments NO synthesis leading to suppression of platelet thrombus formation.

The influence of dietary bacillus natto productive protein (BNPP) on endogenous thrombolysis was investigated in the rat. Animals were given a standard feed for 14 weeks, to which 0.2 or 1% BNPP was added. Thrombolysis was evaluated using an He-Ne laser-induced thrombosis model in mesenteric microvessels. Changes in thrombus volume, reflecting thrombolysis, decreased to 82% of the initial value in the control group. In contrast, the thrombus volume decreased to 67% in the animals fed 0.2% BNPP, and decreased to 51% in the group given 1% BNPP. The extent of thrombolysis in the 1% BNPP group was equivalent to that seen in animals treated with a bolus intravenous infusion of 0.2 mg/kg tissue plasminogen activator. The results demonstrated that the dietary administration of BNPP enhanced endogenous thrombolysis in a dose-dependent manner. Argatroban (2 mg/kg/h) enhanced endogenous fibrinolysis only in control animals, but not in the BNPP groups. The results support the suggestion that dietary supplementation with BNPP may provide a simple means to promote fibrinolysis not only in the treatment of thromboembolism but also in the prevention of venous occlusion.