Abstract
Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underlying CIH-exaggerated post-MI remodeling remains unclear. In this study, we used RNA-sequencing to construct the expression profiles of cardiac mRNAs, microRNAs, and long non-coding RNAs (lncRNA) in four groups of C57BL/6J mice (Sham, CIH, MI, MI + CIH) to evaluate how CIH regulates cardiac remodeling after MI. Compared with the other three groups, the MI + CIH group exhibited 345 lncRNAs, 35 microRNAs, and 5,220 differentially expressed mRNAs. Further analysis showed that CIH led to significant changes in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed mRNAs. Co-expression network analysis identified two core lncRNAs (Mirt1 and AC125351.1) and two core microRNAs (miR-466i-5p and miR-574-5p) during the development of CIH-exaggerated post-MI remodeling, and they were verified by quantitative real-time PCR (qRT-PCR). LncRNA-mRNA correlation analysis further showed that lncRNA Mirt1 was positively correlated with Apbb1ip and Lcp2. In addition, microRNA-mRNA correlation analysis showed that microRNA miR-466i-5p was positively correlated with Snai2, Cdc27, and Ngfr. Furthermore, combining with lncRNA-mRNA and miRNA-mRNA networks, 44 RNAs were identified in the competitive endogenous RNA (ceRNA) network. Mirt1 acts as a ceRNA to bind to miR-466i-5p to further regulate the expression levels of the target gene, thereby aggravating cardiac remodeling after MI. In conclusion, our study provides a systematic perspective on the potential functions of mRNAs, microRNAs, and lncRNAs in CIH-exaggerated post-MI cardiac remodeling. Our data suggest that lncRNA Mirt1 may be the most critical regulator of MI aggravated by CIH.
Highlights
The incidence of myocardial infarction (MI) has increased rapidly over recent years, and the mortality rate associated with MI has steadily increased in the past 10 years (Yeghiazarians et al, 2021)
The effect of Chronic intermittent hypoxia (CIH) on the expression profiles of long non-coding RNAs (lncRNA), microRNAs, and mRNAs, in MI mice and whether specific lncRNAs or microRNA are critical for CIH-exaggerated post-MI cardiac remodeling remains to be elucidated
CeRNA analysis suggested that microRNA miR-466i5p and lncRNA Mirt1 may be the most critical transcriptional regulators in the cardiac remodeling that occurs after MI
Summary
The incidence of myocardial infarction (MI) has increased rapidly over recent years, and the mortality rate associated with MI has steadily increased in the past 10 years (Yeghiazarians et al, 2021). Despite advances in reperfusion therapy and the fact that various measures have been taken to control traditional cardiovascular risk factors (smoking, hypertension, dyslipidemia, and diabetes), the incidence and mortality rate of MI have not been reduced effectively. This suggests that other risk factors may have serious effects on the prognosis of patients with MI. Chronic intermittent hypoxia (CIH) is the main feature of OSA and is known to exaggerate cardiac remodeling after MI (Du et al, 2020). The specific contribution of CIH to overall OSA-induced pathological complications, and the transcriptomic mechanisms underlying cardiac remodeling after MI that causes the exaggeration of CIH, remain very unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
