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


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.


CONCLUSIONS
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.
Kada
Nanae
N
Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Suzuki
Toru
T
Aizawa
Kenichi
K
Matsumura
Takayoshi
T
Ishibashi
Naoto
N
Suzuki
Naomi
N
Takeda
Norifumi
N
Munemasa
Yoshiko
Y
Sawaki
Daigo
D
Ishikawa
Takashi
T
Nagai
Ryozo
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000254:growth & development*; D018168:Receptors, Retinoic Acid; D012176:Retinoids / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism
D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082925:retinoic acid receptor beta