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To clarify the physiological roles of CD36 as an oxidized low density lipoprotein (OxLDL) receptor, we analyzed the monocyte-derived macrophages from normal and two CD36-deficient subjects, since we identified the molecular abnormalities (

Background: Resistance to modern adjuvant treatment is in part due to the failure of programmed cell death. Therefore the molecules that execute the apoptotic program are potential targets for the development of anti-cancer therapeutics. The sigma-2 receptor has been found to be over-expressed in some types of malignant tumors, and, recently, small molecule ligands to the sigma-2 receptor were found to induce cancer cell apoptosis.

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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CLEC-2 has been described recently as playing crucial roles inClec-2 ؉/؉ embryos, we were able to demonstrate that CLEC-2 is involved in thrombus stabilization in vitro and in vivo, possibly through homophilic interactions without apparent increase in bleeding tendency. We propose that CLEC-2 could be an ideal novel target protein for an anti-platelet drug, which inhibits pathological thrombus formation but not physiological hemostasis.

Congenital macrothrombocytopenia is a genetically heterogeneous group of rare disorders. ␣IIb␤3 has not been implicated in these conditions. We identified a novel, conserved heterozygous ITGA2B R995W mutation in 4 unrelated families. The surface expression of platelet ␣IIb␤3 was decreased to 50% to 70% of control. There was spontaneous PAC-1 and fibrinogen binding to resting platelets without CD62p expression. The activation state of ␣IIb␤3 in 293T cells was higher for ␣IIb-W995 than for ␤3-H723 but was weaker than for ␤3-