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Trichostatin A enhances proliferation and migration of vascular smooth muscle cells by downregulating thioredoxin 1
- Trichostatin A enhances proliferation and migration of vascular smooth muscle cells by downregulating thioredoxin 1
- Song S.; Kang S.W.; Choi C.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Cardiovascular Research
- Cardiovascular Research vol. 85, no. 1, pp. 241 - 249
- SCIE; SCOPUS
- Document Type
- AimsA reduction in the level of thioredoxin 1 (Trx1) has been proposed as a possible mechanism for the tumor-specific growth arrest caused by inhibition of histone deacetylases (HDACs). In this study, we investigated the effect of trichostatin A (TSA), a potent HDAC inhibitor, on the proliferation and migration of vascular smooth muscle cells (VSMCs), and we examined the role of reduced Trx1 levels in this effect.Methods and resultsTSA treatment time-dependently decreased Trx1 expression in rat VSMCs at both the mRNA and protein levels. It also enhanced platelet-derived growth factor (PDGF)-induced proliferation and migration of the VSMCs. By potentiating Akt phosphorylation, the siRNA-induced downregulation of Trx1 also enhanced VSMC proliferation and migration in response to PDGF or serum treatment. Consistent with these results, TSA administration increased neointimal thickening in a murine model of post-angioplastic restenosis.ConclusionThese data demonstrate that TSA enhances vascular proliferative activity by downregulating Trx1, thus activating an Akt-dependent pathway. Our results indicate that, in addition to its apoptotic effects in tumour cells, the downregulation of Trx1 has a proliferative role in primary VSMCs.
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