mRNA, lncRNA, and circRNA expression profiles in a new aortic dissection murine model induced by hypoxia and Ang II

Yuanyuan Li; Xiaozhu Ma; Shuai Mei; Yueping Ji; Dong Wang; Liqun He; Dating Sun; Jiangtao Yan

doi:10.3389/fcvm.2022.984087

mRNA, lncRNA, and circRNA expression profiles in a new aortic dissection murine model induced by hypoxia and Ang II

Front Cardiovasc Med. 2022 Oct 26:9:984087. doi: 10.3389/fcvm.2022.984087. eCollection 2022.

Authors

Yuanyuan Li^{1

2}, Xiaozhu Ma¹, Shuai Mei¹, Yueping Ji³, Dong Wang³, Liqun He³, Dating Sun^{1

3}, Jiangtao Yan¹

Affiliations

¹ Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Cardiology, Wuhan No. 1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China.

Abstract

Background and aims: Aortic dissection (AD) is a cardiovascular emergency with degeneration of the aortic media. Mounting evidence indicates obstructive sleep apnea (OSA) as an independent risk factor for AD development with unknown mechanisms. This study aims to establish a stable murine model of OSA-related AD (OSA-AD) and uncover the potential changes in gene transcripts in OSA-AD.

Materials and methods: ApoE^-/- mice were exposed to the chronic intermittent hypoxia (CIH) system combined with Ang II administration to establish the OSA-AD model. Pathological staining was performed to exhibit the physiological structure of the mouse aorta. The SBC mouse ceRNA microarray was used to identify significantly differentially expressed (DE) mRNAs, DE long-non-coding RNAs (DElncRNAs), and DE circular RNAs (DEcircRNAs) in OSA-AD tissues. Subsequently, bioinformatics analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and protein-protein interaction (PPI) analyses, were performed to evaluate the function of the significantly differentially expressed transcripts (DETs). The hub genes were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: ApoE^-/- mice exposed to CIH and Ang II showed a high ratio of aortic accident (73.33%) and significant aortic diameter dilatation (1.96 ± 0.175 mm). A total of 1,742 mRNAs, 2,625 lncRNAs, and 537 circRNAs were identified as DETs (LogFC ≥ 1.5 or ≤ -1.5, P < 0.05). GO and KEGG analyses demonstrated that the differentially expressed mRNAs (DEmRNAs) were most enriched in cell proliferation, migration, apoptosis, inflammation, and hypoxia-related terms, which are closely related to aortic structural homeostasis. The PPI network contained 609 nodes and 934 connections, the hub genes were highlighted with the CytoHubba plugin and confirmed by qRT-PCR in AD tissues. KEGG pathway analysis revealed that the cis-regulated genes of DElncRNAs and circRNAs-host genes were enriched in aortic structural homeostasis-related pathways.

Conclusion: Our findings help establish a de novo OSA-AD animal model using ApoE^-/- mice. Many DEmRNAs, DElncRNAs, and DEcircRNAs were screened for the first time in OSA-AD tissues. Our findings provide useful bioinformatics data for understanding the molecular mechanism of OSA-AD and developing potential therapeutic strategies for OSA-AD.

Keywords: aortic dissection; aortic structure; apoptosis; bioinformatics; hypoxia; inflammation; obstructive sleep apnea.