Cilostazol Induces Metallothionein Expression in Vascular Cells

Abstract

Metallothionein (MT) is a cysteine-rich low molecular weight protein and thought to function in the detoxification of heavy metals and reactive oxygen species. We examined the induction of MT synthesis by cilostazol, an antiplatelet drug, in several vascular component cells to find a new pharmacological effect of cilostazol in vascular system. In human coronary artery endothelial cells, cilostazol significantly increased MT-IX and MT-IIA mRNA levels after the treatment for 6 h and endogenous MT-I/II protein levels after the treatment for 24 and 48 h. In addition, cadmium cytotoxicity was prevented by cilostazol in this endothelial cells. Moreover, cilostazol increased MT-IX and MT-IIA mRNA levels in human coronary artery smooth muscle cells, human brain microvascular endothelial cells, human brain microvascular pericytes and human colon carcinoma Caco-2 cells after the treatment for 6 h. Interestingly, cilostazol also increased MT-III mRNA level in brain microvascular endothelial cells more effectively than in other vascular cells. The present results suggest that cilostazol can protect the vascular system from toxic substances such as heavy metals via MT induction in vascular cells.