Antithrombic and anti-atherogenic effects of partially defatted flaxseed meal using a laser-induced thrombosis test in apolipoprotein E and low-density lipoprotein receptor deficient mice

Sano, Takashi; Oda, Etsuko; Yamashita, Takatoshi; Shiramasa, Hiroshi; Ijiri, Yoshinobu; Yamashita, Tsutomu; Yamamoto, Junichiro

doi:10.1097/00001721-200312000-00003

Cited by 19 publications

(19 citation statements)

References 29 publications

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“…Our findings that dietary flaxseed can inhibit the development of atherosclerotic plaques on the aortic luminal surface are consistent with previous reports (41,52,54,59,64). Because dietary flaxseed supplementation did not alter circulating cholesterol levels, either in the presence or in the absence of additional cholesterol in the diet (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…Flaxseed is a good source of soluble and insoluble dietary fiber and is the richest plant source of ␣-linolenic acid [ALA; C18:3 n-3, omega-3 (n-3) fatty acid] as well as the lignan secoisolariciresinol diglucoside (SDG) (39,53,68). Whole ground flaxseed or the derivatized components of flaxseed have exhibited cardioprotective and anti-atherogenic properties both clinically (7,8,12,32,42,47) and in several animal models (41,52,54,56,59,62,64,71,76). However, these results were observed using rather short periods of cholesterol feeding.…”

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confidence: 99%

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Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

Dupasquier

Weber

Ander

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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-Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol-and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the antiatherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions. linseed; acetylcholine; nutrition; polyunsaturated fatty acids; vascular relaxation ATHEROSCLEROSIS IS THE leading cause of cardiovascular morbidity and mortality in North America (77). Atherosclerosis induces two significant pathological processes: an ischemic event due to blood flow obstruction and vascular contractile dysfunction. It is well known that atherosclerosis is associated with elevated circulating cholesterol levels. Elevated plasma cholesterol concentrations induced by cholesterol feeding result in the development of atherosclerosis and an impairment in endothelium-dependent vasodilation in rabbits (9,26,29,30,36). The development of interventions to inhibit cholesterolinduced atherosclerosis and the associated vascular dysfunction have received much attention because of this strong association. For example, there is an increasing interest in nutritional interventions that may prevent the development of atherosclerosis and protect against the vascular function abnormalities induced by cholesterol consumption. Flaxseed is one such novel dietary intervention. Flaxseed is a good source of soluble and insoluble dietary fiber and is the richest plant source of ␣-linolenic acid [ALA; C18:3 n-3, omega-3 (n-3) fatty acid] as well as the lignan secoisolariciresinol digluco...

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

Dupasquier

Weber

Ander

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…15 The tail of anesthetized mice (nembutal 65 mg/kg; 8 to 12 weeks old) was transected 5 mm from the tip and then immersed in 0.9% isotonic saline at 37°C. The point until complete cessation of bleeding was defined as the bleeding time.…”

Section: Assessment Of Atherosclerosis and Bleeding Time Measurementmentioning

confidence: 99%

“…15 Anesthetized mice (nembutal 65 mg/kg) were placed onto a microscope stage, and the left carotid artery (450 to 500 m in diameter) was gently exposed. Evans blue dye (20 mg/kg) was injected into the left femoral artery via an indwelt tube, and then the center of the exposed carotid artery was irradiated with a laser beam (200 m in diameter at the focal plane) from a He-Ne laser (Model NEO-50MS; Nihon Kagaku Engineering Co, Ltd).…”

Section: He-ne Laser-induced Thrombosismentioning

confidence: 99%

Adiponectin Acts as an Endogenous Antithrombotic Factor

Kato¹,

Kashiwagi²,

Shiraga³

et al. 2006

ATVB

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170

116

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Objective-Obesity is a common risk factor in insulin resistance and cardiovascular diseases. Although hypoadiponectinemia is associated with obesity-related metabolic and vascular diseases, the role of adiponectin in thrombosis remains elusive. Methods and Results-We investigated platelet thrombus formation in adiponectin knockout (APN-KO) male mice (8 to 12 weeks old) fed on a normal diet. There was no significant difference in platelet counts or coagulation parameters between wild-type (WT) and APN-KO mice. However, APN-KO mice showed an accelerated thrombus formation on carotid arterial injury with a He-Ne laser (total thrombus volume: 13.36Ϯ4.25ϫ10 7 arbitrary units for APN-KO and 6.74Ϯ2.87ϫ10 7 arbitrary units for WT; nϭ10; PϽ0.01). Adenovirus-mediated supplementation of adiponectin attenuated the enhanced thrombus formation. In vitro thrombus formation on a type I collagen at a shear rate of 250 s Ϫ1 , as well as platelet aggregation induced by low concentrations of agonists, was enhanced in APN-KO mice, and recombinant adiponectin inhibited the enhanced platelet aggregation. In WT mice, adenovirus-mediated overexpression of adiponectin additionally attenuated thrombus formation. Key Words: acute coronary syndromes Ⅲ obesity Ⅲ platelets Ⅲ thrombosis O besity is associated with insulin resistance, accelerated atherothrombosis, and cardiovascular diseases. 1,2 Recent studies have revealed that adipose tissue is not only a passive reservoir for energy storage but also produces and secretes a variety of bioactive molecules, known as adipocytokines, including tumor necrosis factor (TNF) ␣, leptin, resistin, and plasminogen activator inhibitor type-1. [2][3][4] Dysregulated production of adipocytokines participates in the development of obesityrelated metabolic and vascular diseases. [2][3][4] Adiponectin is an adipocytokine identified in the human adipose tissue cDNA library, and Acrp30/AdipoQ is the mouse counterpart of adiponectin (reviewed in reference 5 ). Adiponectin, of which mRNA is exclusively expressed in adipose tissue, is a protein of 244 amino acids consisting of 2 structurally distinct domains, an N-terminal collagen-like domain and a C-terminal complement C1q-like globular domain. Adiponectin is abundantly present in plasma (5 to 30 g/mL), and its plasma concentration is inversely related to the body mass index. 5 Plasma adiponectin levels decrease in obesity, type 2 diabetes, and patients with coronary artery disease (CAD). 5-9 Indeed, adiponectin (APN) knockout (KO) mice showed severe diet-induced insulin resistance. 10 In cultured cells, we have demonstrated that human recombinant adiponectin inhibited the expression of adhesion molecules on endothelial cells, the transformation of macrophages to foam cells, and TNF-␣ production from macrophages. 5,11 Furthermore, APN-KO mice showed severe neointimal thickening in mechanically injured arteries. 12 Adenovirusmediated supplementation of adiponectin attenuated the development of atherosclerosis in apolipoprotein E-deficient mice as well as postinj...

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“…Details of this technique have been described elsewhere [13] . After perfusion fixation, the whole length of aorta was removed, fixed further in 10% neutral buffered formalin for 24 h, opened up longitudinally, pinned out on a black rubber sheet and stained with oil red O (Sigma-Aldrich Japan, Tokyo, Japan).…”

Section: Severity Of Atherosclerosismentioning

confidence: 99%

Mechanism of the Antithrombotic Effect of Dietary Diacylglycerol in Atherogenic Mice

Ijiri¹,

Naemura²,

Yamashita³

et al. 2006

Pathophysiol Haemos Thromb

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Introduction: We have shown earlier that diacylglycerol (DAG) but not triacylglycerol (TAG) inhibited thrombus formation. The aim of the present study was to investigate the mechanism of this antithrombotic effect of DAG. Materials and Methods: Four different diets, the (1) Western-style high-fat diet (HFD) containing 20% lipid and 0.05% cholesterol (w/w), (2) TAG-rich and (3) DAG-rich HFDs containing 20% lipid and 0.05% cholesterol, but all lipid replaced by TAG or DAG oil with very similar fatty acid composition and the (4) Japanese-style low-fat diet (LFD) containing 7% oil but no cholesterol were given to apolipoprotein E and low-density lipoprotein (LDL) receptor double-deficient mice. Atherogenicity was assessed by morphology, mapping the whole aorta and measuring the total area of lipid-stained lesions. Endothelial function was measured by the flow-mediated vasodilation test. Platelet reactivity was assessed from native blood sample by a shear-induced platelet function test (hemostatometry). Serum lipoprotein profile was measured by HPLC. Results: Both the Western-style and the TAG-rich HFDs have accelerated atherosclerosis. In contrast, DAG-rich HFD inhibited the atherosclerotic process to an extent comparable with the Japanese-style LFD. There was no significant difference in platelet and coagulant activity between the studied diet groups. DAG-rich but not the TAG-rich HFD significantly suppressed serum LDL cholesterol level. Conclusions: The present findings suggest that the mechanism of antithrombotic and anti-atherogenic effect of DAG may involve the protection of the vascular endothelium from injury and lowered serum LDL cholesterol.

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Antithrombic and anti-atherogenic effects of partially defatted flaxseed meal using a laser-induced thrombosis test in apolipoprotein E and low-density lipoprotein receptor deficient mice

Cited by 19 publications

References 29 publications

Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

Adiponectin Acts as an Endogenous Antithrombotic Factor

Mechanism of the Antithrombotic Effect of Dietary Diacylglycerol in Atherogenic Mice

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