MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages.

Abstract:

BACKGROUND:Accumulating evidence suggests that microRNA-590 (miR-590) has protective effects on cardiovascular diseases, but the mechanism is unknown. Interestingly, previous studies from our laboratory and others have shown that macrophage-derived lipoprotein lipase (LPL) might accelerate atherosclerosis by promoting lipid accumulation and inflammatory response. However, the regulation of LPL at the post-transcriptional level by microRNAs has not been fully understood. In this study, we explored whether miR-590 affects the expression of LPL and its potential subsequent effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. METHODS AND RESULTS:Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-590 directly inhibited LPL protein and mRNA expression by targeting LPL 3'UTR. LPL Activity Assays showed that miR-590 reduced LPL activity in the culture media. Oil Red O staining and high-performance liquid chromatography assays showed that miR-590 had inhibitory effects on the lipid accumulation in human THP-1 macrophages. We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. With the method of small interfering RNA, we found that LPL siRNA can inhibit the miR-590 inhibitor-induced increase in lipid accumulation and secretion of pro-inflammatory cytokines in oxLDL-treated human THP-1 macrophages. CONCLUSIONS:MiR-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting LPL gene in human THP-1 macrophages. Therefore, targeting miR-590 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.

journal_name

Biochimie

journal_title

Biochimie

authors

He PP,Ouyang XP,Tang YY,Liao L,Wang ZB,Lv YC,Tian GP,Zhao GJ,Huang L,Yao F,Xie W,Tang YL,Chen WJ,Zhang M,Li Y,Wu JF,Peng J,Liu XY,Zheng XL,Yin WD,Tang CK

doi

10.1016/j.biochi.2014.08.003

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

81-90

eissn

0300-9084

issn

1638-6183

pii

S0300-9084(14)00221-1

journal_volume

106

pub_type

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