miRNA-29a inhibits atherosclerotic plaque formation by mediating macrophage autophagy via PI3K/AKT/mTOR pathway

Abstract

Background: miR-29a plays a vital role in AS, but the relationship between the miR-29a-targeted PI3K signaling pathway and AS remains unclear. Therefore, this study was carried out. Methods: Gene expression profiles from the GEO database containing AS samples were analyzed. ApoE −/− mice and RAW264.7 cells were treated with miR-29a negative control (NC), miR-29a mimic and miR-29a inhibitor to establish the AS model. Then MOVAT staining, TEM, Western blotting, and immunofluorescence staining were adopted for testing target proteins. Results: DEGs were identified from GSE137578, GSE132651, GSE113969, GSE43292, and GSE97210 datasets. It was found that there were targeted binding sites between miR-29a and PIK3CA. Besides, GO and KEGG analysis demonstrated that autophagy was an enriched pathway in AS. Later, PPI network was depicted, and hub genes were then determined. The results revealed that miR-29a suppressed the areas of plaques and lesional macrophages, but had no impact on VSMCs. TEM results showed the organelles pyknosis of lesional macrophages damaged morphological changes. Furthermore, miR-29a amplified the M2-like macrophages but suppressed the polarization of M1-like macrophages in atherosclerotic plaques. According to mouse and RAW 264.7 cell experiments, miR-29a significantly inhibited the protein expressions of PI3K, p-PI3K, p-AKT, and p-mTOR, which were consistent with the increased expressions of autophagy-related proteins, Beclin 1 and LC3II. However, the miR-29a suppression exhibited the contrary results. Conclusion: MiR-29a elevation induces the increase of autophagy by down-regulating the PI3K/AKT/mTOR pathway in the progression of AS, indicating that miR-29a is a novel therapeutic strategy for AS.

miR‐29a‐3p promotes the regulatory role of eicosapentaenoic acid in the NLRP3 inflammasome and autophagy in microglial cells

“…The authors thought that these findings may be related to the different pathological conditions of the diseases. In the present work, miR‐29a‐3p was downregulated in LPS‐stimulated BV2 cells, and its restoration strikingly alleviated inflammatory responses and NLRP3 inflammasome by enhancing autophagy, which was similar to Shao et al's report 29 . Moreover, bioinformatics software analysis and literature showed that miR‐29a‐3p was related to CpG‐mediated DNA methylation 32 .…”

“…Furthermore, miR‐29a‐3p was also reported as an autophagy regulator in various diseases. For example, miR‐29a‐3p was confirmed to inhibit macrophage polarization toward the M2 type and activate autophagy in atherosclerosis via the PI3K/AKT/mTOR pathway 29 . In contrast, miR‐29a‐3p aggravated pathological cardiac hypertrophy and ulcerative colitis by repressing autophagy 30,31 .…”

Exosomal miR-133a-3p Derived from BMSCs Alleviates Cerebral Ischemia-Reperfusion Injury via Targeting DAPK2

“… 27 , 28 In addition, Beclin-1 played a key role in progression of autophagy. 29 Hence, our finding revealed that exosomal miR-133a-3p derived from BMSCs could inhibit the progression of CI/R injury via mediation of Beclin-1 and Akt/mTOR signaling.…”

Upgulation of lncRNA GASL1 inhibits atherosclerosis by regulating miR-106a/LKB1 axis

“…Vascular endothelial cells are the protective barrier of vascular intima, and their damage or dysfunction can lead to an increase in intimal permeability, intimal dysfunction, and AS [ 15 ]. Although the mechanism of AS has been deeply studied, as a genetic susceptibility disease, the research on transcriptome level can fully explain the pathogenesis and provide opportunities for developing new biomarkers and treatments [ 16 ]. Thus, it is of great significance to analyze the influencing factors and pathogenesis of AS.…”