ABCA1 and ABCG1 expressions are regulated by statins and ezetimibe in Caco-2 cells
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Fabiana D.V. Genvigir
,
Alice C. Rodrigues
Abstract
Background: Enterocytes play a crucial role in high-density lipoprotein (HDL) biogenesis. Statins and ezetimibe are potent lowering-cholesterol drugs, which can also influence HDL plasma concentrations. We hypothesized that these drugs could modulate the expression of intestinal ABCA1and ABCG1, two genes involved in HDL metabolism.
Methods: Caco-2 cells were used as a model of the human intestinal cells and were treated with statins (0.01–1 μmol/L) and/or ezetimibe (0.5–5.0 μmol/L) for 12 h or 24 h. Gene expression was examined using real-time PCR.
Results: ABCA1 level was more abundant than ABCG1 in Caco-2 cells. ABCA1 was downregulated after 12-h and 24-h treatment with atorvastatin (0.1 and 1.0 μmol/L) or simvastatin (0.01, 0.1 and 1 μmol/L) (p<0.05). In statin-treated cells, ABCG1 levels remained unaltered. Ezetimibe alone did not induce change of ABCA1 or ABCG1 mRNA levels (p>0.05) but 24-h ezetimibe (2.5 or 5.0 μmol/L) plus simvastatin (1 μmol/L) treatment decreased the transcription of ABCA1 and ABCG1 (p<0.05).
Conclusions: Our findings reveal that, at the concentrations studied, statins isolated or combined with ezetimibe, but not ezetimibe alone, downregulate ABCA1 mRNA expression in Caco-2 cells. Moreover, simvastatin combined with ezetimibe treatment also decrease the ABCG1 levels in these cells.
©2011 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Editorial
- Pharmacogenomics and drug interactions. A specific journal
- Publisher's Note
- Publisher's Note
- Reviews
- Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine
- Effect of apolipoprotein E polymorphism on statin-induced decreases in plasma lipids and cardiovascular events
- Minireview
- Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions
- Original Article
- Biological and genetic factors associated with ABCB1 and pregnane-X-receptor expressions in peripheral blood mononuclear cells in the STANISLAS cohort
- Short Communications
- ABCA1 and ABCG1 expressions are regulated by statins and ezetimibe in Caco-2 cells
- Tumor necrosis factor-α and interleukin-6 expression in leukocytes and their association with polymorphisms and bone markers in diabetic individuals treated with pioglitazone
- Short Report
- From systems biology and functional genomics to personalized health
