title: ABCA1 and ABCG1 expressions are regulated by statins and ezetimibe in Caco-2 cells.
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 ABCA1 and 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.
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil. fdallavecchia@yahoo.com.br
authors.forename: Fabiana D V
authors.initials: FD
authors.lastname: Genvigir
authors.forename: Alice C
authors.initials: AC
authors.lastname: Rodrigues
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cerda
authors.forename: Mario H
authors.initials: MH
authors.lastname: Hirata
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Rosario D C
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology*; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011758:Pyrroles; D012333:RNA, Messenger / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D001384:Azetidines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin; D019821:Simvastatin; D000069438:Ezetimibe