Alpha 2.0

» Articles » PMID: 33411680

Overexpression of Long Noncoding RNA ANRIL Inhibits Phenotypic Switching of Vascular Smooth Muscle Cells to Prevent Atherosclerotic Plaque Development

Overview

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Jan 7

PMID 33411680

Citations 13

Authors

Authors

Da-Jun Hu

Zhen-Yu Li

Yuan-Ting Zhu

Chuan-Chang Li

Affiliations

Affiliations

Soon will be listed here.

Abstract

Background: Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a key role in atherosclerosis. Long noncoding RNA ANRIL (lncRNA-ANRIL) is critical in vascular homeostasis. Metformin produces multiple beneficial effects in atherosclerosis. However, the underlying mechanisms need to be elucidated.

Methods And Results: Metformin increased lncRNA-ANRIL expression and AMPK activity in cultured VSMCs, and inhibited the phenotypic switching of VSMCs to the synthetic phenotype induced by platelet-derived growth factor (PDGF). Overexpression of lncRNA-ANRIL inhibited phenotypic switching and reversed the reduction of AMPK activity in PDGF-treated VSMCs. While, gene knockdown of lncRNA-ANRIL by adenovirus or silence of AMPKγ through siRNA abolished AMPK activation induced by metformin in VSMCs. RNA-immunoprecipitation analysis indicated that the affinity of lncRNA-ANRIL to AMPKγ subunit was increased by metformin. , administration of metformin increased the levels of lncRNA-ANRIL, suppressed VSMC phenotypic switching, and prevented the development of atherosclerotic plaque in mice fed with western diet. These protective effects of metformin were abolished by infecting mice with adenovirus expressing lncRNA-ANRIL shRNA. The levels of AMPK phosphorylation, AMPK activity, and lncRNA-ANRIL expression were decreased in human atherosclerotic lesions.

Conclusion: Metformin activates AMPK to suppress the formation of atherosclerotic plaque through upregulation of lncRNA-ANRIL.

Citing Articles

Recent Advances in the Mutual Regulation of m6A Modification and Non-Coding RNAs in Atherosclerosis.

Wang Y, Ling S, Feng H, Hua J, Han Z, Chai R Int J Gen Med. 2025; 18:1047-1073.

PMID: 40026815 PMC: 11871936. DOI: 10.2147/IJGM.S508197.

Targeting PDGF/PDGFR Signaling Pathway by microRNA, lncRNA, and circRNA for Therapy of Vascular Diseases: A Narrow Review.

Ma C, Shi S, Zhang X, Xin G, Zou X, Li W Biomolecules. 2024; 14(11).

PMID: 39595622 PMC: 11592287. DOI: 10.3390/biom14111446.

Differentiation and Growth-Arrest-Related lncRNA (): Initial Characterization in Human Smooth Muscle and Fibroblast Cells.

de la Cruz-Thea B, Natali L, Ho-Xuan H, Bruckmann A, Coll-Bonfill N, Strieder N Int J Mol Sci. 2024; 25(17).

PMID: 39273443 PMC: 11394763. DOI: 10.3390/ijms25179497.

LncRNAs are involved in regulating ageing and age-related disease through the adenosine monophosphate-activated protein kinase signalling pathway.

Li J, Xiao F, Wang S, Fan X, He Z, Yan T Genes Dis. 2024; 11(5):101042.

PMID: 38966041 PMC: 11222807. DOI: 10.1016/j.gendis.2023.06.014.

CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1.

Huang X, Fu F, Qian K, Feng Q, Cao S, Wu W Mol Cell Biochem. 2024; 480(1):203-215.

PMID: 38409514 DOI: 10.1007/s11010-024-04932-2.

References

1.

Lin H, Ni T, Zhang J, Meng L, Gao F, Pan S . Knockdown of Herp alleviates hyperhomocysteinemia mediated atherosclerosis through the inhibition of vascular smooth muscle cell phenotype switching. Int J Cardiol. 2018; 269:242-249. DOI: 10.1016/j.ijcard.2018.07.043. View

2.

McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox D . A common allele on chromosome 9 associated with coronary heart disease. Science. 2007; 316(5830):1488-91. PMC: 2711874. DOI: 10.1126/science.1142447. View

3.

Witters L, Kemp B . Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'-AMP-activated protein kinase. J Biol Chem. 1992; 267(5):2864-7. View

4.

Kim J, Yang G, Kim Y, Kim J, Ha J . AMPK activators: mechanisms of action and physiological activities. Exp Mol Med. 2016; 48:e224. PMC: 4855276. DOI: 10.1038/emm.2016.16. View

5.

Bierhoff H . Analysis of lncRNA-Protein Interactions by RNA-Protein Pull-Down Assays and RNA Immunoprecipitation (RIP). Methods Mol Biol. 2017; 1686:241-250. DOI: 10.1007/978-1-4939-7371-2_17. View

6.

Yang J, Li P, Wang F, Liang W, Ma H, Chen Y . Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo. Oncotarget. 2016; 7(33):52729-52739. PMC: 5288144. DOI: 10.18632/oncotarget.10400. View

7.

Zhou S, Lu J, Wang X, Shan M, Miao Z, Pan G . S-Nitrosylation of Prostacyclin Synthase Instigates Nitrate Cross-Tolerance In Vivo. Clin Pharmacol Ther. 2018; 105(1):201-209. DOI: 10.1002/cpt.1094. View

8.

Griffin S, Leaver J, Irving G . Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017; 60(9):1620-1629. PMC: 5552849. DOI: 10.1007/s00125-017-4337-9. View

9.

Libby P . Inflammation in atherosclerosis. Nature. 2002; 420(6917):868-74. DOI: 10.1038/nature01323. View

10.

Wang S, Zhang C, Zhang M, Liang B, Zhu H, Lee J . Activation of AMP-activated protein kinase α2 by nicotine instigates formation of abdominal aortic aneurysms in mice in vivo. Nat Med. 2012; 18(6):902-10. PMC: 3559018. DOI: 10.1038/nm.2711. View

11.

Wang F, Xu C, He Q, Cai J, Li X, Wang D . Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population. Nat Genet. 2011; 43(4):345-9. DOI: 10.1038/ng.783. View

12.

Shaw R, Kosmatka M, Bardeesy N, Hurley R, Witters L, DePinho R . The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004; 101(10):3329-35. PMC: 373461. DOI: 10.1073/pnas.0308061100. View

13.

Zhang H, Liu M, Lu J, Zhu M, Jin Q, Ping S . Intracellular acidosis via activation of Akt-Girdin signaling promotes post ischemic angiogenesis during hyperglycemia. Int J Cardiol. 2018; 277:205-211. DOI: 10.1016/j.ijcard.2018.08.028. View

14.

Hunter R, Hughey C, Lantier L, Sundelin E, Peggie M, Zeqiraj E . Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase. Nat Med. 2018; 24(9):1395-1406. PMC: 6207338. DOI: 10.1038/s41591-018-0159-7. View

15.

Hawley S, Davison M, Woods A, DAVIES S, Beri R, Carling D . Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem. 1996; 271(44):27879-87. DOI: 10.1074/jbc.271.44.27879. View

16.

Wang T, Chen K, Hsu P, Lin H, Wang Y, Chen C . microRNA let-7g suppresses PDGF-induced conversion of vascular smooth muscle cell into the synthetic phenotype. J Cell Mol Med. 2017; 21(12):3592-3601. PMC: 5706591. DOI: 10.1111/jcmm.13269. View

17.

Ferre F, Colantoni A, Helmer-Citterich M . Revealing protein-lncRNA interaction. Brief Bioinform. 2015; 17(1):106-16. PMC: 4719072. DOI: 10.1093/bib/bbv031. View

18.

Vasamsetti S, Karnewar S, Kanugula A, Thatipalli A, Kumar J, Kotamraju S . Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes. 2015; 64(6):2028-41. DOI: 10.2337/db14-1225. View

19.

Holdt L, Teupser D . Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol. 2012; 32(2):196-206. DOI: 10.1161/ATVBAHA.111.232678. View

20.

Gopoju R, Panangipalli S, Kotamraju S . Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis. Free Radic Biol Med. 2018; 118:85-97. DOI: 10.1016/j.freeradbiomed.2018.02.031. View