Author:
Le Tianming,He Xin,Huang Jianhua,Liu Shuai,Bai Yang,Wu Kemin
Abstract
Abstract
Background
Abdominal aortic aneurysm (AAA), an irreversible cardiovascular disease prevalent in the artery, causes the increase of the aneurysm diameter over time, and is a fatal phenomenon inducing sidewall rupture. Long noncoding RNAs (lncRNAs) serve as promising biomarkers for AAA. In the present study, we sought to define the role of lncRNA growth-arrest-specific transcript 5 (GAS5) in growth of smooth muscle cells (SMC) and progression of AAA.
Methods
Initially, we established angiotensin II (Ang II)-induced AAA mouse models and Ang II-treated vascular SMC model. RT-qPCR and Western blot analysis were adopted to determine expression of GAS5 and zeste homolog 2 (EZH2). After ectopic expression and depletion experiments in Ang II-treated mice and vascular SMCs, cell apoptosis was detected in SMCs using flow cytometry and in mice using TUNEL staining. The binding of GAS5 and EZH2 was evaluated using RNA binding protein immunoprecipitation (RIP) and Co-IP assays.
Results
Increased GAS5 and RIG-I but decreased EZH2 were found in aortic tissues of AAA mice. EZH2 overexpression inhibited AAA formation and suppressed SMC apoptosis. Functionally, EZH2 blocked the RIG-I signaling pathway and consequently inhibited SMC apoptosis. GAS5 regulated EZH2 transcription in a negative manner in SMCs. Knockdown of GAS5 attenuated SMC apoptosis, which was reversed by EZH2 inhibition or RIG-I overexpression.
Conclusions
The current study demonstrated that GAS5 induced SMC apoptosis and subsequent AAA onset by activating EZH2-mediated RIG-I signaling pathway, highlighting GAS5 as a novel biomarker for AAA.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference39 articles.
1. Li J, Pan C, Zhang S, Spin JM, Deng A, Leung LLK, et al. Decoding the genomics of abdominal aortic aneurysm. Cell. 2018;174:1361-72.e10.
2. Liu Y, Wang TT, Zhang R, Fu WY, Wang X, Wang F, et al. Calorie restriction protects against experimental abdominal aortic aneurysms in mice. J Exp Med. 2016;213:2473–88.
3. Li R, Yi X, Wei X, Huo B, Guo X, Cheng C, et al. EZH2 inhibits autophagic cell death of aortic vascular smooth muscle cells to affect aortic dissection. Cell Death Dis. 2018;9:180.
4. Ullery BW, Hallett RL, Fleischmann D. Epidemiology and contemporary management of abdominal aortic aneurysms. Abdom Radiol. 2018;43:1032–43.
5. Aggarwal S, Qamar A, Sharma V, Sharma A. Abdominal aortic aneurysm: a comprehensive review. Exp Clin Cardiol. 2011;16:11–5.
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