Trichostatin A enhances proliferation and migration of vascular smooth muscle cells by downregulating thioredoxin 1

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Aims A 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 results TSA 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. Conclusion These 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.
Publisher
OXFORD UNIV PRESS
Issue Date
2010-01
Language
English
Article Type
Article
Keywords

HISTONE DEACETYLASE INHIBITORS; HUMAN ASTROGLIAL CELLS; NECROSIS-FACTOR-ALPHA; BINDING PROTEIN-2; KAPPA-B; APOPTOSIS; CANCER; DIFFERENTIATION; ACTIVATION; EXPRESSION

Citation

CARDIOVASCULAR RESEARCH, v.85, no.1, pp.241 - 249

ISSN
0008-6363
DOI
10.1093/cvr/cvp263
URI
http://hdl.handle.net/10203/96791
Appears in Collection
BiS-Journal Papers(저널논문)
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