Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 241-249 |
| Number of pages | 9 |
| Journal | Cardiovascular Research |
| Volume | 85 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2010 |
Bibliographical note
Funding Information:This research was supported by a grant from the Korea Health 21 R&D Project (A060687) of the Ministry of Health and Welfare, Republic of Korea (to C.C.) and 21C Frontier Functional Proteomics Project (FPR08-B1-190) of Ministry of Education, Science & Technology (to S.W.K.). Funding to pay the Open Access publication charges for this article was provided by Chung Moon Soul Center for Bio-Information and Electronics.
Keywords
- Histone deacetylases
- Migration
- Proliferation
- Thioredoxin
- Vascular smooth muscle cells