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

Author(s)

Cerda, Alvaro ^[1] ; Genvigir, Fabiana Dalla Vecchia ^[1] ; Rodrigues, Alice Cristina ^[1] ; Vieira Willrich, Maria Alice ^[1] ; Dorea, Egidio Lima ^[2] ; Silveira Bernik, Marcia Martins ^[2] ; Arazi, Simone Sorkin ^[1] ; de Oliveira, Raquel ^[1] ; Hirata, Mario Hiroyuki ^[1] ; Crespo Hirata, Rosario Dominguez ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Univ Hosp, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS; v. 18, n. 8, p. 640-651, 2011.
• Web of Science Citations: 9

Abstract

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. (AU)

• FAPESP's process: 09/15125-8 - Influence of cholesterol synthesis and absorption on expression of proteins of the cholesterol reverse transport in HepG2 and CACO-2 cells
• Grantee: Rosario Dominguez Crespo Hirata
• Support Opportunities: Regular Research Grants