Current molecular medicine · 2023
ABCG1 is Expressed in an LXR-Independent Manner in Patients with Type 2 Diabetes Mellitus.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Hui-Juan, Wang Ji-Hong, Xu Xin-Na, Zhao Xing-Shan, Liu Wei
Аннотация
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.
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.