microRNA-125b-1-3p mediates autophagy via the RRAGD/mTOR/ULK1 signaling pathway and mitigates atherosclerosis progression

Authors:

Xin Chen, Yanhong Cao, Yining Guo, Jing Liu, Xiaohan Ye, Huan Li, Lu Zhang, Wenwei Feng, Shaoxiang Xian, Zhongqi Yang, Lingjun Wang, Ting Wang

Keywords:

Atherosclerosis, miR-125b-1-3p, Autophagic activity, RRAGD/mTOR/ULK1 pathway

Abstract:

Atherosclerosis is characterised by lipid accumulation and formation of foam cells in arterial walls. Dysregulated autophagy is a crucial factor in atherosclerosis development. The significance of microRNA (miR)-125b-1-3p in cardiovascular disease is well-established; however, its precise role in regulating autophagy and impact on atherosclerosis in vascular smooth muscle cells (VSMCs) remain unclear. Here, we observed reduced autophagic activity and decreased miR-125b expression during atherosclerosis progression. miR-125b-1-3p overexpression significantly reduced atherosclerotic plaque development in mice; it also led to decreased lipid uptake and deposition in VSMCs, enhanced autophagy, and suppression of smooth muscle cell phenotypic changes in-vitro. An interaction between miR-125b-1-3p and the RRAGD/mTOR/ULK1 pathway was revealed, elucidating its role in promoting autophagy. Therefore, miR-125b-1-3p plays a pivotal role in enhancing autophagic processes, inhibiting foam cell formation in VSMCs and mitigating atherosclerosis progression, partly through RRAGD/mTOR/ULK1 signaling axis modulation. Thus, miR-125b-1-3p is a promising target for preventive and therapeutic strategies for atherosclerosis.

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