Elsevier

Nutrition

Volume 19, Issue 3, March 2003, Pages 261-264
Nutrition

Basic nutritional investigation
Dietary supplementation with fermented soybeans suppresses intimal thickening

https://doi.org/10.1016/S0899-9007(02)00853-5Get rights and content

Abstract

Although soy foods have been consumed for more than 1000 y, it is only in the past 20 y that they have made inroads into Western diets. We investigated the effect of dietary supplementation with natto extracts produced from fermented soybeans on intimal thickening of arteries after vessel endothelial denudation. Natto extracts include nattokinase, a potent fibrinolytic enzyme having four times greater fibrinolytic activity than plasmin. Intimal thickening was induced in the femoral arteries by intravenous infusion of rose bengal followed by focal irradiation with a transluminal green light. Dietary natto extract supplementation was started 3 wk before endothelial injury and continued for another 3 wk after. In ex vivo studies, euglobulin clot lysis times were measured 3 wk after the initial supplementation. Neointima formation and thickening were also initiated successfully. The intima media ratio 3 wk after endothelial injury was 0.15 ± 0.03 in the control group. Dietary natto extract supplementation suppressed intimal thickening (0.06 ± 0.01; P < 0.05) compared with the control group. Natto extracts shortened euglobulin clot lysis time, suggesting that their thrombolytic activities were enhanced. These findings suggest that natto extracts, because of their thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of mural thrombi formation.

Introduction

Many studies, over several decades, have been carried out to analyze the influence of diet habit on both generation and reduction of atherosclerosis.1, 2 Since the incidence of cardiovascular disease in Asia is very low, traditional foods from Asia have been the subject of much attention.3, 4 For more than 1000 y, people throughout Asia have been consuming soybeans in a variety of traditional soy food products.5 Westerners have wholeheartedly adopted some of these products, whereas others will undoubtedly take more time to accept. The most popular soy foods in Western countries are tofu, soy milk (tonyu), soy burger, soy sauce, and miso. Natto, a traditional fermented vegetable cheeselike food, is another soy product. Natto extracts are known to include nattokinase (NK), a potent fibrinolytic enzyme having an approximately four-times stronger activity than plasmin on clot lysis assay.6 It is composed of 275 amino acid residues (molecular weight = 27 728 Da) and exhibits a high homology with subtilisins.7 It has been reported that NK detected by its antibody was absorbed across rat intestinal tract after intraduodenal administration and then cleaved fibrinogen in plasma.8 Its remarkable thrombolytic efficacy also was shown in a chemically induced thrombosis model.9

Intravascular thrombus formation causes a variety of cardiovascular diseases,10, 11 in which abnormalities of platelet aggregation, coagulation system, and/or dysfunction of vascular endothelial cells play an important role. In recent years, intimal thickening and restenosis of arteries have become a major drawback in arterial reconstruction for atherosclerotic and thrombotic diseases. An important basic process for intimal thickening is the migration of smooth muscle cells from the media to the intima and their subsequent proliferation. In the process, platelet-derived growth factor released from the adherent platelets and cytokines from accumulated leukocytes are reported to play key roles by initiating the migration and proliferation of smooth muscle cells.12

We have recently developed a model of intimal thickening following vascular endothelial injury. In this model, we damage a small segment of vascular endothelium by a focally produced reactive oxygen species through photochemical reaction between a green light and a dye, rose bengal (RB). This photochemical reaction induces a thrombogenic condition at the site of endothelial injury without medial injury.13, 14 Using this model, we have investigated the effects of extracts obtained from natto by using a powdered product adjusted to be 50 times greater in NK activity than those of commercial products on intimal thickening and thrombogenesis in the rat femoral artery.

Section snippets

Preparation of natto extracts

One gram of crude natto extract needed 8.4 g of commercial natto. The commercial natto (17.5 kg; Kinnotsubu-fukumaro, Freshia Company Ltd., Ibaragi, Japan) was suspended in iron-exchanged water (87.5 L) at 4°C. After 21 h, the suspension was filtered, and the water-soluble extract was lyophilized to make a powder.

Animals and diets

Twenty-four male Sprague-Dawley rats (5 wk old; SLC, Hamamatsu, Japan) were assigned to one of two groups: control or treatment with a dietary supplementation of natto extracts (Table I

Inhibitory effect of natto extracts on intimal thickening

Twenty-one days after intimal denudation, significant intimal thickening was observed in the subendothelial layer in control animals, as previously reported.17 Dietary natto extract supplementation suppressed intimal thickening (Fig. 1). The results of the morphometric analysis are shown in Fig. 2. The cross-sectional area of the intima in the injured femoral arteries in the control group was 1.21 ± 0.16 (× 0.01 mm2). Dietary natto extract supplementation significantly reduced the area to

Discussion

Arteriosclerosis is a chronic process and frequently induces lethal vascular diseases including myocardial and cerebral infarctions. Much effort has been expended to establish strategies to prevent its progression. Some strategies, such as low-fat intakes or periodic physical exercise, are effective in lowering the risk for myocardial infarction. In this study, we investigated the effect of dietary natto extract supplementation on arterial intimal thickening after endothelial injury. We found

Acknowledgements

The authors thank Mr. H. Osugi for technical assistance.

References (30)

  • R. Ross et al.

    The biology of platelet-derived growth factor

    Cell

    (1986)
  • S.M. Artaud-Wild et al.

    Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox

    Circulation

    (1993)
  • M. Fujita et al.

    Transport of nattokinase across the rat intestinal tract

    Biol Pharm Bull

    (1995)
  • M. Fujita et al.

    Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat

    Biol Pharm Bull

    (1995)
  • V. Fuster et al.

    The pathogenesis of coronary artery disease and the acute coronary syndromes (1)

    N Engl J Med

    (1992)
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