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

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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.