Modulation of microRNA Expression in Subjects with Metabolic Syndrome and Decrease of Cholesterol Efflux from Macrophages via microRNA-33-Mediated Attenuation of ATP-Binding Cassette Transporter A1 Expression by Statins

Metabolic syndrome (MetS) is a complicated health problem that encompasses a variety of metabolic disorders. In this study, we analyzed the relationship between the major biochemical parameters associated with MetS and circulating levels of microRNA (miR)-33, miR-103, and miR-155. We found that miRN...

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Bibliographic Details
Published in:PloS one 2016-05, Vol.11 (5), p.e0154672-e0154672
Main Authors: Chen, Wei-Ming, Sheu, Wayne H-H, Tseng, Pei-Chi, Lee, Tzong-Shyuan, Lee, Wen-Jane, Chang, Pey-Jium, Chiang, An-Na
Format: Article
Language:English
Subjects:
3' Untranslated regions
ABC transporters
ABCA1 protein
Abnormalities
Analysis
Animals
Atherosclerosis
Atorvastatin
ATP
ATP Binding Cassette Transporter 1 - genetics
ATP-binding protein
Biochemistry
Biological Transport - drug effects
Biology and Life Sciences
Bone marrow
Cardiovascular disease
Cholesterol
Cholesterol - metabolism
Complications and side effects
Development and progression
Diabetes
Dosage and administration
Down-Regulation - drug effects
Down-Regulation - genetics
Drugs
Efflux
Endocrinology
Federal regulation
Female
Gastroenterology
Gene expression
Gene Expression Regulation - drug effects
Gene Expression Regulation - genetics
Gene regulation
Genetic aspects
Glucose
Glucose - pharmacology
Hemoglobin
Hepatology
High density lipoprotein
Homeostasis
Homeostasis - drug effects
Hospitals
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Hyperglycemia
Internal medicine
Low density lipoprotein
Macrophages
Macrophages - drug effects
Macrophages - metabolism
Male
Medicine
Medicine and Health Sciences
Metabolic disorders
Metabolic syndrome
Metabolic Syndrome - genetics
Metabolic Syndrome - metabolism
Metabolic syndrome X
Mice
MicroRNA
MicroRNAs
MicroRNAs - genetics
Middle Aged
miRNA
Modulation
Molecular biology
Physical Sciences
Physiological aspects
Post-transcription
Proteins
RAW 264.7 Cells
Ribonucleic acid
RNA
Statins
Systemic diseases
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Summary:Metabolic syndrome (MetS) is a complicated health problem that encompasses a variety of metabolic disorders. In this study, we analyzed the relationship between the major biochemical parameters associated with MetS and circulating levels of microRNA (miR)-33, miR-103, and miR-155. We found that miRNA-33 levels were positively correlated with levels of fasting blood glucose, glycosylated hemoglobin A1c, total cholesterol, LDL-cholesterol, and triacylglycerol, but negatively correlated with HDL-cholesterol levels. In the cellular study, miR-33 levels were increased in macrophages treated with high glucose and cholesterol-lowering drugs atorvastatin and pitavastatin. miR-33 has been reported to play an essential role in cholesterol homeostasis through ATP-binding cassette transporter A1 (ABCA1) regulation and reverse cholesterol transport. However, the molecular mechanism underlying the linkage between miR-33 and statin treatment remains unclear. In the present study, we investigated whether atorvastatin and pitavastatin exert their functions through the modulation of miR-33 and ABCA1-mediated cholesterol efflux from macrophages. The results showed that treatment of the statins up-regulated miR-33 expression, but down-regulated ABCA1 mRNA levels in RAW264.7 cells and bone marrow-derived macrophages. Statin-mediated ABCA1 regulation occurs at the post-transcriptional level through targeting of the 3'-UTR of the ABCA1 transcript by miR-33. Additionally, we found significant down-regulation of ABCA1 protein expression in macrophages treated with statins. Finally, we showed that high glucose and statin treatment significantly suppressed cholesterol efflux from macrophages. These findings have highlighted the complexity of statins, which may exert detrimental effects on metabolic abnormalities through regulation of miR-33 target genes.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0154672