Acyclic retinoid inhibits neointima formation through retinoic acid receptor beta-induced apoptosis
Acyclic retinoid inhibits neointima formation through retinoic acid receptor beta-induced apoptosis
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DOI：
10.1161/atvbaha.106.134114
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发表时间：
2007-07-01
影响因子：
8.7
通讯作者：
Nagai, Ryozo
中科院分区：
文献类型：
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作者：
Kada, Nanae;Suzuki, Toru;Nagai, Ryozo
目标 - 无环类视黄醇 (ACR) 是一种具有高安全性的合成类视黄醇，人们对它在预防（复发）和治疗恶性肿瘤方面的治疗用途抱有很高的期望。为了解决心血管系统中的治疗潜力，即新内膜形成，研究了ACR对新内膜形成的影响以及所涉及的机制。方法和结果-将ACR给予袖带损伤的小鼠，其显示出对新内膜形成的抑制。在细胞和分子水平上对相关机制的研究表明，ACR 诱导新内膜细胞凋亡，这是通过选择性诱导视黄酸受体 β (RAR β) 介导的，RAR β 对平滑肌细胞具有生长抑制和促凋亡作用。结论 - 我们表明，ACR 通过诱导 RAR β 抑制新内膜形成，RAR β 反过来又抑制细胞生长并诱导细胞凋亡。类视黄醇 ACR 可能可用于治疗和预防新内膜形成。
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( RAR beta) which shows growth inhibitory and proapoptotic effects on smooth muscle cells.Conclusion - We show that ACR inhibits neointima formation by inducing RAR beta which in turn inhibits cell growth and induces apoptosis. The retinoid, ACR, may be potentially exploitable for treatment and prevention of neointima formation.