MiR-520a-3p Inhibited Macrophage Polarization and Promoted the Development of Atherosclerosis via Targeting UVRAG in Apolipoprotein E Knockout Mice

Abstract

Atherosclerosis (AS), a kind of chronic inflammatory blood vessel disease, is a main cause of cardiovascular disease, which is a leading cause of mortality around the world. Accumulation of macrophages induced by inflammation contributes to AS development. It has been indicated that microRNAs (miRNAs) are involved in the process of AS. However, the pathway and gene miRNAs targeting are poorly understood. Here we reported that miR-520a-3p was increased in mice with AS and silencing of miR-520a-3p attenuated AS process. Furthermore, inhibition of miR-520a-3p increased the expression of α-SMA and collagen. In addition, miR-520a-3p silencing inhibited the expression of M1 macrophage polarization markers and pro-inflammatory genes and promoted the M2 macrophage polarization. What’s more, forced expression of miR-520a-3p diminished IL4/IL13 induced macrophage autophagy via targeting UVRAG. Collectively, our study reveals the role of miR-520a-3p in macrophage polarization and suggests the potential of miRNA as a novel treatment target of AS.

A Bibliometric and Knowledge-Map Analysis of Macrophage Polarization in Atherosclerosis From 2001 to 2021

“…We conclude that the hotspots of macrophage polarization in AS initially focused on its impact on obesity. Studies explored more critical targets in this area, including Nrf2 ( 59 ), Kruppel-like factor 4 ( 60 – 63 ), GLP-1/GLP-1R ( 64 ), TLR4 ( 27 , 65 ), and micro RNA ( 66 , 67 ), related to inflammation process and plaque progression. Cardiovascular disease studies, including the role of macrophage polarization in lipid metabolism, inflammatory immune response in plaques, and cerebrovascular disease, are two diseases involved in this field.…”

Comprehensive view of macrophage autophagy and its application in cardiovascular diseases

“…89 Forced expression of miR-520a-3p dampens the expression of LC3 and degradation of p62 to retard IL-4-triggered M2 differentiation through the interaction with 3 0 untranslated region of UVRAG to accelerate the progression of AS (Figure 4). 90 Notably, the cell composition of the plaques is intricate at different stages. Macrophages predominate during early atherosclerotic plaques; however, foam cells take over in the late stages and transition from macrophages by phagocytizing lipids.…”

The Regulatory Role of Non-coding RNA in Autophagy in Myocardial Ischemia-Reperfusion Injury

“…LncRNA Xist upregulated the expression of STX17 via inhibiting miR-23b-3p/miR-29a-3p ( Liu H. et al, 2020 ). Moreover, miR-520a-3p ( Qi et al, 2020 ), miR-216b ( Luo et al, 2018 ), and miR-125a ( Kim et al, 2015 ) regulated autophagy by targeting UVRAG. Therefore, it is speculated that these non-coding RNAs play an important role in promoting the fusion of autophagosomes and lysosomes.…”