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...

The prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet may be an important risk factor for thrombotic events. The daily intake of an anti-thrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test tomato extracts for anti-thrombotic effects and to identify those varieties that have such an effect. A shear-induced platelet-function test (haemostatometry) was used to test anti-thrombotic potential in vitro. Extracts from those tomato varieties that showed a significant anti-thrombotic activity in vitro were further assessed in vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99-4) showed significant anti-thrombotic activity both in vitro and in vivo. KG99-4 inhibited not only platelet-rich thrombus formation but also had a thrombolytic effect. It is concluded that haemostatometry can detect and classify the anti-thrombotic potential of fruits and vegetables and offers a simple way of screening for such effects.

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Resveratrol is one of the major polyphenolics in red wine that has been shown to exert the preventive effects against cardiovascular diseases. The effect of trans-resveratrol (t-RES) administered as an ingredient of the diet on the atherothrombotic tendency was assessed in genetically hypercholesterolemic mice after laser-induced damage on endothelium. Mice lacking both apolipoprotein E and low-density lipoprotein receptor (apoE-/-/LDLR-/-) were fed with a high-fat diet with or without t-RES (9.6 and 96 mg/kg diet) for 8 weeks. The atherosclerotic tendency was morphometrically analyzed in their aortae. The thrombotic tendency was determined by inducing thrombus by the irradiation of a helium-neon laser on carotid arteries of these mice with injection of Evans blue. Atherosclerotic area and thrombus size were evaluated by image analyzing in a computer system. Even though the plasma concentrations of lipids (total cholesterol and triacylglycerol) did not change in the control and t-RES groups, a significant decrease (approximately 30%) in the formation of atheroma was observed in the aortae of the t-RES group. The size of laser-induced thrombus that mostly consisted of platelet aggregates was significantly reduced (approximately 25%) in the t-RES group compared with that in the control group. Thus, t-RES orally administrated with a high-fat diet in apoE-/-/LDLR-/- mice significantly suppressed atherosclerosis in their aortae and reduced the laser-induced thrombosis in their carotid arteries.

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