PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice.
Genes Cells
; 21(10): 1030-1048, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27545963
ABSTRACT
Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe-/- ) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch+/+ Apoe-/- and Prkch-/- Apoe-/- mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch+/+ Apoe-/- mice was improved in Prkch-/- Apoe-/- mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch+/+ Apoe-/- mice, was improved in Prkch-/- Apoe-/- mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch-/- Apoe-/- mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch-/- Apoe-/- mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch-/- Apoe-/- macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe-/- mice, showing that PKCη plays a role in atherosclerosis development.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
/
Proteína Quinase C
/
Aterosclerose
/
Metabolismo dos Lipídeos
Limite:
Animals
Idioma:
En
Revista:
Genes Cells
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão