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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1535.)
© 2007 American Heart Association, Inc.

Vascular Biology

Acyclic Retinoid Inhibits Neointima Formation Through Retinoic Acid Receptor Beta-Induced Apoptosis

Nanae Kada; Toru Suzuki; Kenichi Aizawa; Takayoshi Matsumura; Naoto Ishibashi; Naomi Suzuki; Norifumi Takeda; Yoshiko Munemasa; Daigo Sawaki; Takashi Ishikawa; Ryozo Nagai

From the Departments of Cardiovascular Medicine (N.K., T.S., K.A., T.M., N.T., Y.M., D.S., R.N.), Clinical Bioinformatics (T.S.), and Gastroenterology (T.I.), The University of Tokyo, and Pharmaceutical Research Laboratories (N.I., N.S.), Nikken Chemicals Co, Saitama, Japan.

Correspondence to Toru Suzuki or Ryozo Nagai, Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. E-mail torusuzu-tky{at}umin.ac.jp or nagai-tky@umin.ac.jp

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 ß (RARß) which shows growth inhibitory and proapoptotic effects on smooth muscle cells.

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

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.

Key Words: smooth muscle cell • cell growth • retinoid

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