Expression and activity of ABCG2, but not ABCB1 or OATP1B1, are associated with cholesterol levels: evidence from in vitro and in vivo experiments

Aim: This study investigated whether cholesterol levels influence the expression and function of drug transporters and whether statin treatments could alter this by reducing plasma low-density lipoprotein cholesterol levels. Patients & methods: The mRNA expression and function of OATP1B1, ABCB1 and ABCG2 were assessed in peripheral blood mononuclear cells (PBMCs) of healthy subjects and from patients with familial hypercholesterolemia (FH) before and after statin treatment by real-time PCR and flow cytometric assay, respectively. The effects of statin exposure and cholesterol depletion in PBMCs and in cell lines were assessed. Results: ABCG2 expression and activity in PBMCs in patients with FH were 2-fold and 26-fold higher, respectively, than those of the healthy subjects (p < 0.001 for both). Statin treatment decreased ABCG2 expression and function in patients with FH. Depletion of cholesterol ex vivo reduced ABCG2 expression in PBMCs and reduced ABCG2 activity in liver and colon cells. Conclusion: This study suggested that statins may downregulate ABCG2 expression and function through reducing low-density lipoprotein cholesterol levels.