Predominance of a proinflammatory phenotype in monocyte-derived macrophages from subjects with low plasma HDL-cholesterol.
Arterioscler Thromb Vasc Biol
; 27(5): 1115-22, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17322100
ABSTRACT
OBJECTIVE:
Reduced plasma concentrations of high-density lipoprotein-cholesterol (HDL-C) are a significant risk factor for cardiovascular disease. Mechanisms that regulate HDL-C concentrations represent an important area of investigation. METHODS ANDRESULTS:
Comparative transcriptome analyses of monocyte-derived macrophages (MDM) from a large population of low HDL-C subjects and age- and sex-matched controls revealed a cluster of inflammatory genes highly expressed in low HDL-C subjects. The expression levels of peroxisome proliferator activated receptor (PPAR) gamma and several antioxidant metallothionein genes were decreased in MDM from all low HDL-C groups compared with controls, as was the expression of other genes regulated by PPARgamma, including CD36, adipocyte fatty acid binding protein (FABP4), and adipophilin (ADFP). In contrast, PPARdelta expression was increased in MDM from low HDL-C groups. Quantitative RT-PCR corroborated all major findings from the microarray analysis in two separate patient cohorts. Expression of several inflammatory cytokine genes including interleukin 1beta, interleukin 8, and tumor necrosis factor alpha were highly increased in low HDL-C subjects.CONCLUSIONS:
The activated proinflammatory state of monocytes and MDM in low HDL-C subjects constitutes a novel parameter of risk associated with HDL deficiency, related to altered expression of metallothionein genes and the reciprocal regulation of PPARgamma and PPARdelta.
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Base de dados:
MEDLINE
Assunto principal:
RNA
/
Expressão Gênica
/
PPAR delta
/
PPAR gama
/
Hipolipoproteinemias
/
HDL-Colesterol
/
Macrófagos
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Canadá