MiR-188-3p upregulation results in the inhibition of macrophage proinflammatory activities and atherosclerosis in ApoE-deficient mice.

Abstract:

BACKGROUND:Atherosclerosis occurs as a result of a chronic inflammatory response in the arterial wall associated with an increased uptake of low-density lipoprotein by macrophages and the subsequent transformation of this lipoprotein into foam cells. It has been found that miR-188-3p can suppress autophagy and myocardial infarction. Therefore, we conducted the present study with determining the suppressive role played by miR-188-3p in atherosclerosis. METHODS:The atherosclerosis model was established using ApoE knockout mice. The healthy C57BL/6J wide-type mice were used as control, while miR-188-3p mimics or inhibitors were applied for the elevation or the depletion of the miR-188-3p expression in mice. The macrophage content was observed in atherosclerotic plaque. Once the miR-188-3p expression was determined, the effects of the over-expression of miR-188-3p on the lipid accumulation and macrophage inflammatory response were accessed. The plasma levels of pro-inflammatory factors and serum RANTES level, as well as OLR1, iNOS, ABCA1 and KLF2 expression were determined in order to evaluate the potential anti-inflammatory and antioxidative activities of miR-188-3p. RESULTS:ApoE knockout mice with atherosclerosis presented with increased lipid accumulation and macrophage content. MiR-188-3p was found to reduce intravascular lipid accumulation in atherosclerotic mice. In addition to the alleviation of macrophage inflammatory response, the upregulation of miR-188-3p also leads to the suppression of oxidation with reduced macrophage accumulation, plasma expression of pro-inflammatory factors and serum RANTES level, OLR1 and iNOS, while it increases ABCA1 and KLF2. CONCLUSIONS:In conclusion, the findings from our study found a new potential therapy for atherosclerosis by investigating the inhibitory effects of miR-188-3p on macrophage inflammatory response and oxidation.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Zhang XF,Yang Y,Yang XY,Tong Q

doi

10.1016/j.thromres.2018.09.043

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

55-61

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(18)30527-9

journal_volume

171

pub_type

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