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ABCG1 is Expressed in an LXR-Independent Manner in Patients with Type 2 Diabetes Mellitus
Ist Teil von
Current molecular medicine, 2023-01, Vol.23 (8), p.815-824
Erscheinungsjahr
2023
Beschreibungen/Notizen
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 a pivotal role in the regulation of cholesterol
efflux. However, the regulation of these transporters in type 2 diabetes mellitus remains
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 into 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 were
detected by electrophoretic mobility supershift assay.
Results:
Macrophage ATP-binding cassette G1 expression and high density lipoproteininduced
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 receptorindependent
pathway.