Role of metallothionein on the progression of atherosclerosis and its application to medical care.

由于金属硫蛋白（MT）具有抗氧化应激和炎症的保护作用，我们认为血管组织中的MT可能有助于防止动脉粥样硬化的发展。在本研究中，我们利用细胞培养系统和动物模型来确定血管组织中的MT是否可以保护动脉粥样硬化的发生和发展。首先，在本研究期间，我们从ApoE敲除小鼠和MT-I和MT-II敲除小鼠产生MT-I、MT-II和载脂蛋白E（ApoE）缺陷小鼠（MT-I/II/Apo-E三重敲除小鼠）。我们还证明了人类血管内皮细胞暴露于砷和镉，这是血管病变的危险因素的基因表达谱。此外，我们发现，抗血小板药物西洛他唑强烈抑制砷和镉在血管内皮细胞中诱导金属硫蛋白合成的血管毒性。这些观察结果表明，MT在血管组织中可能有助于防止动脉粥样硬化的进展。

Since metallothionein (MT) has a protective role against oxidative stress and inflammation, we considered that MT in the vascular tissue may be contribute to the protection against the development of atherosclerosis. In this study, we have utilized cell culture systems and animal models to determine whether MT in the vascular tissue can protect the onset and the progression of atherosclerosis. First, in this study period, we produced the MT-I, MT-II and apolipoprotein E (ApoE) deficient mice (MT-I/II/Apo-E triple-knockout mice) from ApoE knockout mice and MT-I and MT-II knockout mice. We also demonstrated the gene expression profile of human vascular endothelial cells exposed to arsenic and cadmium, which are risk factors for vascular lesions. In addition, we found that anti-platelet drug cilostazol strongly inhibits the vascular toxicity of arsenic and cadmium in vascular endothelial cells as a result of induction of metallothionein synthesis. These observations suggests that MT in the vascular tissue may contribute to the protection against the progression of atherosclerosis.