Influence of Polymorphisms and Cholesterol-Lowering Treatment on SCARB1 mRNA Expression

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art_CERDA_Influence_of_Polymorphisms_and_CholesterolLowering_Treatment_on_SCARB1_2011.PDF (477.75 KB)
Citações na Scopus
13
Tipo de produção
article
Data de publicação
2011
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
JAPAN ATHEROSCLEROSIS SOC
Autores
CERDA, Alvaro
GENVIGIR, Fabiana Dalla Vecchia
RODRIGUES, Alice Cristina
WILLRICH, Maria Alice Vieira
ARAZI, Simone Sorkin
OLIVEIRA, Raquel de
HIRATA, Mario Hiroyuki
HIRATA, Rosario Dominguez Crespo
Citação
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS, v.18, n.8, p.640-651, 2011
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Aim: This study evaluated the influence of polymorphisms and cholesterol-lowering treatments on SCARB1 mRNA expression in peripheral blood mononuclear cells and in HepG2 and Caco-2 cells. Methods: Blood samples were drawn from normolipidemic (NL, n = 166) and hypercholesterolemic (HC, n = 123) individuals to extract DNA and total RNA and to analyze the lipid profile. After a 4-week washout period, 98 HC individuals were treated with atorvastatin (10 mg/day/4 weeks) whereas 25 were treated with ezetimibe (10 mg/day/4 weeks), followed by simvastatin (10 mg/day/8 weeks) and simvastatin plus ezetimibe (10 mg each/day/4 weeks). HepG2 and Caco-2 cells were treated with atorvastatin, simvastatin and ezetimibe at various concentrations for 12 and 24 h and collected for RNA extraction. SCARB1 mRNA expression was measured by TaqMan (R) assay and SCARB1 c.4G > A, c.726 + 54C > T and c.1080C > T polymorphisms were detected by PCR-RFLP. Results: High LDL cholesterol (> 160 mg/dL) values were associated with low baseline SCARB1 mRNA expression in PBMC. Allele T carriers for SCARB1 c.726 + 54C > T had lower basal SCARB1 transcription in PBMC (p < 0.05). Simvastatin, atorvastatin and ezetimibe treatments did not modify the SCARB1 mRNA level in PBMC from HC patients. Similarly, these cholesterol-lowering drugs did not modulate the SCARB1 expression in HepG2 and Caco-2 cells in spite of the concentration and time of exposure (p > 0.05). Conclusion: LDL cholesterol levels and SCARB1 c.726 + 54C > T are associated with low mRNA expression in mononuclear cells. Cholesterol-lowering drugs do not modulate SCARB1 expression in PBMC from HC subjects or in HepG2 and Caco-2 cells.
Palavras-chave
Scavenger receptor class B type I, Cholesterol-lowering drugs, Gene expression, Single nucleotide polymorphisms
URI
https://observatorio.fm.usp.br/handle/OPI/24143
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Coleções
Artigos e Materiais de Revistas Científicas - HU