Rutaecarpine derivative R3 attenuates atherosclerosis via inhibiting NLRP3 inflammasome-related inflammation and modulating cholesterol transport.
FASEB J
; 34(1): 1398-1411, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31914630
ABSTRACT
Atherosclerosis is a chronic disease characterized by lipid deposition and inflammatory response. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-facilitated inflammatory responses are crucial in the pathogenesis of atherosclerosis, and thus new therapeutic approaches are emerging that target NLRP3 and inflammation. Here, we explored the anti-atherosclerotic effect and mechanisms of a new rutaecarpine derivative, 5-deoxy-rutaecarpine (R3) in vitro and in vivo. R3 treatment attenuated atherosclerosis development and increased plaque stability in Apoe-/- mice fed a high-fat diet, and decreased levels of inflammatory mediators, such as interleukin-1ß, in the serum of Apoe-/- mice and in oxidized low-density lipoprotein (ox-LDL)-stimulated murine macrophages. R3 treatment inhibited NLRP3 inflammasome activation in the livers of Apoe-/- mice and ox-LDL-stimulated murine macrophages by inhibiting NF-κB and MAPK pathways. Additionally, R3 significantly decreased total cholesterol in the serum and livers of Apoe-/- mice and promoted cholesterol efflux in murine macrophages through upregulating protein expression of ATP-binding cassette subfamily A member 1 and scavenger receptor class B type I/human CD36 and lysosomal integral membrane protein-II analogous-1. Our results demonstrated that R3 prevented atherosclerotic progression via attenuating NLRP3 inflammasome-related inflammation and modulating cholesterol transport.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinazolinas
/
Colesterol
/
Alcaloides Indólicos
/
Aterosclerosis
/
Inflamasomas
/
Proteína con Dominio Pirina 3 de la Familia NLR
/
Macrófagos
Límite:
Animals
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China