<p>Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA <em>TUG1</em> to Induce Autophagy and Inhibit Atherosclerosis</p>

Abstract

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.

Zisheng Shenqi Decoction Ameliorates Monosodium Urate-Mediated Gouty Arthritis in Rats via Promotion of Autophagy through the AMPK/mTOR Signaling Pathway

“…AMPK/mTOR is the important modulator of cellular autophagy. Hepatic protein kinase B1 is able to activate AMPK in some circumstances such as starvation and energy consumption, which negatively regulates mTOR [ 30 ]. It has been reported that lowered expression of p-mTOR induced by AMPK phosphorylation is capable of facilitating autophagy in a variety of cell types [ 31 ].…”

Activation of Adenosine Monophosphate-activated Protein Kinase by Telmisartan Decreases Basal and Platelet-derived Growth Factor-stimulated Vascular Smooth Muscle Cell Proliferation via Inhibiting the Mammalian Target of Rapamycin/p70 S6 Kinase Signaling Axis

“… 21 Furthermore, AMPK activation by 5-aminoimidazole-4-carboxamide ribonucleotide was reported to inhibit the mTOR/p70S6K signaling pathway in human umbilical vein endothelial cells (HUVECs) and VSMCs. 22 23 Most recently, it was reported that valsartan increased p-AMPK-Thr 172 level and decreased p-mTOR-Ser 2448 level in rat VSMCs 24 ; however, there were somewhat inconsistent time-course results between AMPK activation and mTOR inhibition, i.e., the decreases in p-mTOR-Ser 2448 occurred before the increase in p-AMPK-Thr 172 . 24 Unlike the recently reported data, in the current study, we observed that telmisartan increased AMPK activity first (at 6 hours of treatment) ( Fig.…”

HomeoboxC6 affects the apoptosis of human vascular endothelial cells and is involved in atherosclerosis

“…Rats were randomly divided into high‐fat diet group ( n = 6) and normal feeding group ( n = 6) after adaptive feeding for a week. A rat model of AS was established as previously described (You et al, 2020), and the high‐fat feed ingredients were 80.8% normal diet + 0.2% propylthiouracil + 0.5% sodium cholate + 3.5% cholesterol + 5% sugar + 10% lard. In addition, rats were fed with vitamin D3 (700,000 U/kg) via gavage for three times.…”