RhoA inhibitor-eluting stent attenuates restenosis by inhibiting YAP signaling
RhoA inhibitor-eluting stent attenuates restenosis by inhibiting YAP signaling
复制标题
RhoA 抑制剂洗脱支架通过抑制 YAP 信号传导减轻再狭窄
DOI：
10.1016/j.jvs.2018.04.073
复制
发表时间：
2019-05-01
影响因子：
4.3
通讯作者：
Zheng, Xiaobing
中科院分区：
文献类型：
--
作者：
Huang, Chen;Zhou, Min;Zheng, Xiaobing
目的：目前的药物洗脱支架（DES）治疗是有前途的，但它仍然有支架内再狭窄的缺点，这仍然是一个临床相关的问题。因此，应努力发现新的信号分子和新的潜在靶点来预防动脉再狭窄。在这项研究中，我们制造了一种新的DES针对RhoA通路，并进一步研究了这一有前途的战略在体外和在兔颈动脉model.Methods：主动RhoA表达与合成平滑肌表型，和RhoA抑制剂rhosin抑制这种表型调制在转录和翻译水平。我们进一步证明，RhoA抑制剂rhosin可能通过雅普途径在平滑肌细胞表型调节中起作用。此外，我们制作了一个RhoA支架洗脱支架，并在兔颈动脉model.Results测试：与裸金属支架相比，RhoA支架洗脱支架显着衰减6个月时的新生内膜形成。然而，过表达的雅普的慢病毒阻断了RhoA的载体洗脱支架的抗再狭窄作用和抑制平滑肌特异性genes.Conclusions：RhoA载体洗脱支架衰减新生内膜形成通过抑制的雅普信号通路。这种新型药物洗脱支架可能是治疗支架内再狭窄的一种潜在策略。
Objective: Current drug-eluting stent (DES) treatment is promising, but it still has the drawback of in-stent restenosis, which remains a clinically relevant problem. Efforts should be made to discover new signaling molecules and novel potential targets for the prevention of arterial restenosis. In this study, we fabricated a novel DES targeting the RhoA pathway and further examined this promising strategy in vitro and in a rabbit carotid model.Methods: Active RhoA expression is correlated with the synthetic smooth muscle phenotype, and the RhoA inhibitor rhosin suppresses this phenotypic modulation at both transcriptional and translational levels. We further demonstrated that the RhoA inhibitor rhosin might act through the YAP pathway in smooth muscle cell phenotype modulation by a gain-of-function assay. Moreover, we fabricated a RhoA inhibitor-eluting stent and tested it in a rabbit carotid model.Results: Compared with a bare-metal stent, the RhoA inhibitor-eluting stent significantly attenuated neointimal formation at 6 months. However, overexpression of YAP by lentivirus blocked the antirestenosis effect of the RhoA inhibitor-eluting stent and repressed smooth muscle-specific genes.Conclusions: RhoA inhibitor-eluting stents attenuate neointimal formation through inhibition of the YAP signaling pathway. This novel DES may represent a potential strategy for the treatment of in-stent restenosis.