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 TUG1 ) is still unknown. Thus, this research investigated the effect of metformin and lncRNA TUG1  on AS.
Methods: First, qRT-PCR was used to detect the expression of lncRNA TUG1  in patients with coronary heart disease (CHD). Then, the correlation between metformin and TUG1  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 TUG1  to provide a new strategy for the prevention and treatment of AS.
Results: qRT-PCR results suggested that lncRNA TUG1  expression was robustly upregulated in patients with CHD. In vitro experiments indicated that after metformin administration, the expression of lncRNA TUG1  decreased in a time-dependent manner. Metformin and TUG1  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-TUG1  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 TUG1 .
Keywords: metformin, taurine up-regulated gene 1, AMPK/mTOR, autophagy, atherosclerosis