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Ritonavir increases CD36, ABCA1 and CYP27 expression in THP-1 macrophages.
Pou, Jordi; Rebollo, Alba; Roglans, Núria; Sánchez, Rosa M; Vázquez-Carrera, Manuel; Laguna, Juan C; Pedro-Botet, Juan; Alegret, Marta.
Afiliação
  • Pou J; Pharmacology Department, Faculty of Pharmacy and Biomedicine Institute (IBUB), University of Barcelona, and Ciber Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Instituto de Salud Carlos III, Spain.
Exp Biol Med (Maywood) ; 233(12): 1572-82, 2008 Dec.
Article em En | MEDLINE | ID: mdl-18849545
ABSTRACT
UNLABELLED Ritonavir, a protease inhibitor used in combination antiretroviral therapy for HIV-1 infection, is associated with an increased risk of premature atherosclerosis. The aim of the present study was to assess the effects of ritonavir, in the absence of added lipoproteins, on the expression of genes that control cholesterol trafficking in human monocytes/macrophages.

DESIGN:

THP-1 cells were used to study the effects of ritonavir on the expression of CD36, ATP binding cassette transporters A1 (ABCA1) and G1 (ABCG1), scavenger receptor B class I (SR-BI), caveolin-1 and sterol 27-hydroxylase (CYP27). Exposure to ritonavir (2.5 mug/ml) increased CD36 protein (28%, P < 0.05) and mRNA (38%, P < 0.05) in differentiated THP-1 macrophages, but not in undifferentiated monocytes. This effect was not related to the increase in PPARgamma expression (51%, P < 0.05) caused by ritonavir. Ritonavir also reduced SR-BI protein levels (46%, P < 0.05) and increased CYP27 (43%, P < 0.05) and ABCA1 (49%, P < 0.05) mRNA expression. Liver X receptor alpha (LXRalpha) mRNA, protein and binding activity were also increased by ritonavir treatment.

CONCLUSIONS:

We propose that ritonavir induces ABCA1 expression in THP-1 macrophages through LXRalpha. The increase in ABCA1 and other cholesterol efflux mediators, such as CYP27, may compensate CD36 induction. Therefore, we suggest that the net effect of ritonavir on macrophages in the absence of lipoproteins is not clearly proatherogenic.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Monócitos / Inibidores da Protease de HIV / Transportadores de Cassetes de Ligação de ATP / Antígenos CD36 / Ritonavir / Colestanotriol 26-Mono-Oxigenase Limite: Humans Idioma: En Ano de publicação: 2008 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Monócitos / Inibidores da Protease de HIV / Transportadores de Cassetes de Ligação de ATP / Antígenos CD36 / Ritonavir / Colestanotriol 26-Mono-Oxigenase Limite: Humans Idioma: En Ano de publicação: 2008 Tipo de documento: Article