A selective peroxisome proliferator-activated receptor-ß/δ agonist attenuates neointimal hyperplasia after wire-mediated arterial injury.
Expert Opin Investig Drugs
; 22(9): 1095-106, 2013 Sep.
Article
en En
| MEDLINE
| ID: mdl-23915387
BACKGROUND: Neointimal hyperplasia after the percutaneous coronary intervention is still a clinically serious problem, associated with the risk of thrombosis due to delayed reendothelization. Peroxisome proliferator-activated receptor-ß/δ (PPAR-ß/δ) belongs to a family of ligand-activated transcription factors. OBJECTIVES: In this study, we investigated the effects of GW-0742, a synthetic high-affinity PPAR-ß/δ agonist, on neointimal hyperplasia after arterial injury. Using C57BL/6J mice, we made a wire-injury model and intraperitoneally injected GW-0742 or vehicle once a day. The arteries were harvested for pathological and molecular analysis on day 14 after injury. In vitro, vascular smooth muscle cells (VSMCs), macrophages and human umbilical vein endothelial cells (HUVECs) were cultured, and GW-0742 effects on the cells proliferation were measured. RESULTS: The vehicle-treated injured arteries showed significantly thickened intima, while GW-0742 suppressed it. GW-0742 significantly suppressed IL-6 protein production, the expression of proliferating cell nuclear antigen in the neointima and enhanced CD31 expression. In vitro, GW-0742 attenuated VSMC proliferation triggered by cytokines or macrophages. The drug also induced endothelial regeneration after denudation injury. CONCLUSION: The data suggest that the PPAR-ß/δ agonist is effective for atten- uation of neointimal hyperplasia by suppressing VSMC proliferation and accelerating reendothelization.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiazoles
/
PPAR-beta
/
PPAR delta
/
Neointima
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Expert Opin Investig Drugs
Asunto de la revista:
TERAPIA POR MEDICAMENTOS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido