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

18Citations
Citations of this article
8Readers
Mendeley users who have this article in their library.

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 pmTOR, 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.

Cite

CITATION STYLE

APA

Shao, W., Wang, S., Wang, X., Yao, L., Yuan, X., Huang, D., … Xue, H. (2022). miRNA-29a inhibits atherosclerotic plaque formation by mediating macrophage autophagy via PI3K/AKT/mTOR pathway. Aging, 14(5), 2418–2431. https://doi.org/10.18632/aging.203951

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free