Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA to Induce Autophagy and Inhibit Atherosclerosis.

BACKGROUND

Metformin has been shown to inhibit the proliferation and migration of vascular wall cells. However, the mechanism through which metformin acts on atherosclerosis (AS) via the long non-coding RNA taurine up-regulated gene 1 (lncRNA ) is still unknown. Thus, this research investigated the effect of metformin and lncRNA on AS.

METHODS

First, qRT-PCR was used to detect the expression of lncRNA in patients with coronary heart disease (CHD). Then, the correlation between metformin and expression in vitro and their effects on proliferation, migration, and autophagy in vascular wall cells were examined. Furthermore, in vivo experiments were performed to verify the anti-AS effect of metformin and to provide a new strategy for the prevention and treatment of AS.

RESULTS

qRT-PCR results suggested that lncRNA expression was robustly upregulated in patients with CHD. In vitro experiments indicated that after metformin administration, the expression of lncRNA decreased in a time-dependent manner. Metformin and knockdown via small interfering RNA both inhibited proliferation and migration while promoted autophagy via the AMPK/mTOR pathway in vascular wall cells. In vivo experiments with a rat AS model further demonstrated that metformin and sh- could inhibit the progression of AS.

CONCLUSION

Taken together, our data demonstrate that metformin might function to prevent AS by activating the AMPK/mTOR pathway via lncRNA .