Niacin reduces plasma CETP levels by diminishing liver macrophage content in CETP transgenic mice.
Biochem Pharmacol
; 84(6): 821-9, 2012 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-22750059
The anti-dyslipidemic drug niacin has recently been shown to reduce the hepatic expression and plasma levels of CETP. Since liver macrophages contribute to hepatic CETP expression, we investigated the role of macrophages in the CETP-lowering effect of niacin in mice. In vitro studies showed that niacin does not directly attenuate CETP expression in macrophages. Treatment of normolipidemic human CETP transgenic mice, fed a Western-type diet with niacin for 4 weeks, significantly reduced the hepatic cholesterol concentration (-20%), hepatic CETP gene expression (-20%), and plasma CETP mass (-30%). Concomitantly, niacin decreased the hepatic expression of CD68 (-44%) and ABCG1 (-32%), both of which are specific markers for the hepatic macrophage content. The decrease in hepatic CETP expression was significantly correlated with the reduction of hepatic macrophage markers. Furthermore, niacin attenuated atherogenic diet-induced inflammation in liver, as evident from decreased expression of TNF-alpha (-43%). Niacin similarly decreased the macrophage markers and absolute macrophage content in hyperlipidemic APOE*3-Leiden.CETP transgenic mice on a Western-type diet. In conclusion, niacin decreases hepatic CETP expression and plasma CETP mass by attenuating liver inflammation and macrophage content in response to its primary lipid-lowering effect, rather than by attenuating the macrophage CETP expression level.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Transferencia de Ésteres de Colesterol
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Hígado
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Macrófagos
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Hipolipemiantes
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Niacina
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biochem Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Reino Unido