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.