Disruption of p21-activated kinase 1 gene diminishes atherosclerosis in apolipoprotein E-deficient mice.
Nat Commun
; 6: 7450, 2015 Jun 24.
Article
en En
| MEDLINE
| ID: mdl-26104863
ABSTRACT
Pak1 plays an important role in various cellular processes, including cell motility, polarity, survival and proliferation. To date, its role in atherogenesis has not been explored. Here we report the effect of Pak1 on atherogenesis using atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice as a model. Disruption of Pak1 in ApoE(-/-) mice results in reduced plaque burden, significantly attenuates circulating IL-6 and MCP-1 levels, limits the expression of adhesion molecules and diminishes the macrophage content in the aortic root of ApoE(-/-) mice. We also observed reduced oxidized LDL uptake and increased cholesterol efflux by macrophages and smooth muscle cells of ApoE(-/-)Pak1(-/-) mice as compared with ApoE(-/-) mice. In addition, we detect increased Pak1 phosphorylation in human atherosclerotic arteries, suggesting its role in human atherogenesis. Altogether, these results identify Pak1 as an important factor in the initiation and progression of atherogenesis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
/
Macrófagos Peritoneales
/
Miocitos del Músculo Liso
/
Aterosclerosis
/
Quinasas p21 Activadas
/
Placa Aterosclerótica
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos