Trichostatin A, an Inhibitor of Histone Deacetylase, Inhibits Smooth Muscle Cell Proliferation via Induction of p21WAF1

DOI Web Site PubMed 4 Citations 91 References Open Access
  • Okamoto Hiroshi
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Fujioka Yoshio
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Laboratory of Nutritional Physiology, Faculty of Nutrition, Kobegakuin University
  • Takahashi Akihiro
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Takahashi Tomosaburo
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Taniguchi Takahiro
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Ishikawa Yuichi
    Faculty of Health Sciences, Kobe University School of Medicine
  • Yokoyama Mitsuhiro
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine

Search this article

Description

The proliferation of vascular smooth muscle cells (VSMCs) can contribute to a variety of pathological states, including atherosclerosis and post-angioplasty restenosis. The p21WAF1 cyclin-dependent kinase inhibitor regulates cell-cycle progression, senescence, and differentiation in injured blood vessels. Histone deacetylase (HDAC) inhibitors have shown utility in controlling proliferation in a wide range of tumor cell lines, possibly by inducing the expression of p21WAF1. Our goal was to investigate the effect of trichostatin A (TSA), a specific and potent HDAC inhibitor, on the proliferation of vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta. TSA suppressed the HDAC activity of VSMCs in a dose-dependent manner and inhibited VSMC proliferation as demonstrated by cell number counting and the degree of [3H] thymidine incorporation. Further, TSA reduced the phosphorylation of Rb protein, a regulator of cell-cycle progression. TSA treatment also induced the expression of p21WAF1 but not of p16INK4, p27KIP1 or p53. Finally, TSA inhibited HDAC activity of VSMCs from p21WAF1 knock-out mice but had no effect on VSMC proliferation in these animals. In conclusion, TSA inhibits VSMC proliferation via the induction of p21WAF1 expression and subsequent cell-cycle arrest with reduction of the phosphorylation of Rb protein at the G1-S phase.

Journal

Citations (4)*help

See more

References(91)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top