RhoA inhibitor-eluting stent attenuates restenosis by inhibiting YAP signaling.
J Vasc Surg
; 69(5): 1581-1589.e1, 2019 05.
Article
en En
| MEDLINE
| ID: mdl-31010523
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Orgánicos
/
Angioplastia de Balón
/
Proteínas de Unión al GTP rho
/
Miocitos del Músculo Liso
/
Proliferación Celular
/
Inhibidores Enzimáticos
/
Proteínas Proto-Oncogénicas c-yes
/
Stents Liberadores de Fármacos
/
Músculo Liso Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Vasc Surg
Asunto de la revista:
ANGIOLOGIA
Año:
2019
Tipo del documento:
Article