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Endothelin-1 exacerbates lipid accumulation by increasing the protein degradation of the ATP-binding cassette transporter G1 in macrophages.
J Cell Physiol ; 226(8): 2198-205, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21520072
ABSTRACT
Endothelin-1 (ET-1), a potent proatherogenic vasoconstrictive peptide, is known to promote macrophage foam cell formation via mechanisms that are not fully understood. Excessive lipid accumulation in macrophages is a major hallmark during the early stages of atherosclerotic lesions. Cholesterol homeostasis is tightly regulated by scavenger receptors (SRs) and ATP-binding cassette (ABC) transporters during the transformation of macrophage foam cells. The aim of this study was to investigate the possible mechanisms by which ET-1 affects lipid accumulation in macrophages. Our results demonstrate that oxidized low-density lipoprotein (oxLDL) treatment increases lipid accumulation in rat bone marrow-derived macrophages. Combined treatment with ET-1 and oxLDL significantly exacerbated lipid accumulation in macrophages as compared to treatment with oxLDL alone. The results of Western blotting show that ET-1 markedly decreased the ABCG1 levels via ET type A and B receptors and activation of the phosphatidylinositol 3-kinase pathway; however, ET-1 had no effect on the protein expression of CD36, SR-BI, SR-A, or ABCA1. In addition, real-time PCR analysis showed that ET-1 treatment did not affect ABCG1 mRNA expression. We also found that ET-1 decreases ABCG1 possibly due to the enhancement of the proteosome/calpain pathway-dependent degradation of ABCG1. Moreover, ET-1 significantly reduced the efficiency of the cholesterol efflux in macrophages. Taken together, these findings suggest that ET-1 may impair cholesterol efflux and further exacerbate lipid accumulation during the transformation of macrophage foam cells.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Transportadores de Cassetes de Ligação de ATP / Endotelina-1 / Metabolismo dos Lipídeos / Macrófagos Limite: Animais Idioma: Inglês Revista: J Cell Physiol Ano de publicação: 2011 Tipo de documento: Artigo País de afiliação: Taiwan