ABCG1 is Expressed in a LXR-Independent Manner in Patients with Type 2 Diabetes Mellitus

Abstract

Background:: Patients with type 2 diabetes mellitus have a high cardiovascular risk due, in part, to abnormalities of high-density lipoprotein mediated cholesterol efflux. The ATP-binding cassette A1 and G1 play pivotal role in regulation of cholesterol efflux. However, the regulation of these transporters in type 2 diabetes mellitus remain obscure. Objectives:: This study aimed to investigate the expression of ATP-binding cassette A1 and G1 and their regulation by Liver X receptors in monocyte-derived macrophages in type 2 diabetes mellitus, and to determine whether the alteration of these transporters might affect cholesterol efflux from macrophages. Methods:: Blood was collected from type 2 diabetic patients and healthy controls. Peripheral monocytes were differentiated to macrophages. Quantitative real-time PCR, western blots, and cholesterol efflux assays were performed. The Liver X receptor and Liver X receptor element complex in the ATP-binding cassette G1 gene promoter was detected by electrophoretic mobility supershift assay. Results:: Macrophage ATP-binding cassette G1 expression and high density lipoprotein-induced cholesterol efflux were significantly reduced in type 2 diabetic patients. However, the mRNA expression of ATP-binding cassette G1 in type 2 diabetic patients was not inhibited by Liver X receptor siRNA and the Liver X receptor- Liver X receptor element complexes remain unchanged similarly. Conclusion:: The study suggested that the expression of ATP-binding cassette G1 and high density lipoprotein-induced cholesterol efflux in macrophages were reduced in type 2 diabetes mellitus. Impairment of cholesterol efflux and ATP-binding cassette G1 gene expression in type 2 diabetes mellitus might be regulated by a Liver X receptor-independent pathway.