GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice.
Mol Ther
; 24(11): 1926-1938, 2016 Nov.
Article
en En
| MEDLINE
| ID: mdl-27502608
ABSTRACT
Growth differentiation factor 11 (GDF11) reduces cardiac hypertrophy, improves cerebral vasculature and enhances neurogenesis in ageing mice. Higher growth differentiation factor 11/8 (GDF11/8) is associated with lower risk of cardiovascular events in humans. Here, we showed that adeno-associated viruses-GDF11 and recombinant GDF11 protein improve endothelial dysfunction, decrease endothelial apoptosis, and reduce inflammation, consequently decrease atherosclerotic plaques area in apolipoprotein E-/- mice. Moreover, adeno-associated viruses-GDF11 and recombinant GDF11 stabilize atherosclerotic plaques by selectively decreasing in macrophages and T lymphocytes, while increasing in collagen and vascular smooth muscle cells within plaques. In addition, GDF11 inhibit palmitic acid-induced endothelial apoptosis and ameliorate palmitic acid-induced inflammatory response in RAW264.7 macrophages in vitro. Mechanistically, GDF11 activates the TGF-ß/Smad2/3, AMPK/endothelial nitricoxide synthase (eNOS) while suppresses JNK and NF-κB pathways. In humans, circulating GDF11/8 is positively associated with flow-mediated endothelium-dependent dilation in overweight subjects. We concluded that adeno-associated viruses-GDF11 and recombinant GDF11 protect against endothelial injury and reduce atherosclerosis in apolipoprotein E-/- mice, thus may be providing a novel approach to the treatment of atherosclerosis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
/
Proteínas Recombinantes
/
Terapia Genética
/
Proteínas Morfogenéticas Óseas
/
Células Endoteliales
/
Aterosclerosis
/
Factores de Diferenciación de Crecimiento
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
China