Macrophage adipose triglyceride lipase deficiency attenuates atherosclerotic lesion development in low-density lipoprotein receptor knockout mice.
Arterioscler Thromb Vasc Biol
; 31(1): 67-73, 2011 Jan.
Article
en En
| MEDLINE
| ID: mdl-21030715
ABSTRACT
OBJECTIVE:
The consequences of macrophage triglyceride (TG) accumulation on atherosclerosis have not been studied in detail so far. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for the initial step in TG hydrolysis. Because ATGL knockout (KO) mice exhibit massive TG accumulation in macrophages, we used ATGL KO mice to study the effects of macrophage TG accumulation on atherogenesis. METHODS ANDRESULTS:
Low-density lipoprotein receptor (LDLr) KO mice were transplanted with bone marrow from ATGL KO (ATGL KOâLDLr KO) or wild-type (WTâLDLr KO) mice and challenged with a Western-type diet for 9 weeks. Despite TG accumulation in ATGL KO macrophages, atherosclerosis in ATGL KOâLDLr KO mice was 43% reduced associated with decreased plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage interleukin-6 concentrations. This coincided with a reduced amount of macrophages, possibly because of a 39% increase in intraplaque apoptosis and a decreased migratory capacity of ATGL KO macrophages. The reduced number of white blood cells might be due to a 36% decreased Lin(-)Sca-1(+)cKit(+) hematopoietic stem cell population.CONCLUSIONS:
We conclude that the attenuation of atherogenesis in ATGL KOâLDLr KO mice is due to decreased infiltration of less inflammatory macrophages into the arterial wall and increased macrophage apoptosis.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Triglicéridos
/
Receptores de LDL
/
Hidrolasas de Éster Carboxílico
/
Aterosclerosis
/
Macrófagos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Países Bajos