Acyclic retinoid inhibits neointima formation through retinoic acid receptor beta-induced apoptosis.

Abstract

OBJECTIVES:

Acyclic retinoid (ACR) is a synthetic retinoid with a high safety profile that has been pursued with high expectations for therapeutic use in prevention (recurrence) and treatment of malignancies. With the objective of addressing the therapeutic potential in the cardiovasculature, namely neointima formation, effects of ACR on neointima formation and the involved mechanisms were investigated.

METHODS AND RESULTS:

ACR was administered to cuff-injured mice which showed inhibition of neointima formation. Investigation of involved mechanisms at the cellular and molecular levels showed that ACR induces apoptosis of neointimal cells and this to be mediated by selective induction of retinoic-acid receptor beta (RARbeta) which shows growth inhibitory and proapoptotic effects on smooth muscle cells.

CONCLUSION:

We show that ACR inhibits neointima formation by inducing RARbeta which in turn inhibits cell growth and induces apoptosis. The retinoid, ACR, may be potentially exploitable for treatment and prevention of neointima formation.

• Authors: Nanae Kada, Toru Suzuki, Kenichi Aizawa, Takayoshi Matsumura, Naoto Ishibashi, Naomi Suzuki, Norifumi Takeda, Yoshiko Munemasa, Daigo Sawaki, Takashi Ishikawa, Ryozo Nagai
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 27 Issue 7 Pg. 1535-41 (Jul 2007) ISSN: 1524-4636 [Electronic] United States
• PMID: 17478760 (Publication Type: Journal Article)

Chemical References

• Receptors, Retinoic Acid
• Retinoids
• retinoic acid receptor beta

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Cells, Cultured
• Disease Models, Animal
• Femoral Artery (drug effects, physiology)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (drug effects, growth & development)
• Receptors, Retinoic Acid
• Retinoids (pharmacology)
• Sensitivity and Specificity
• Tunica Intima (drug effects, metabolism)