Circular RNA Expression Profiles and Bioinformatic Analysis in Mouse Models of Obstructive Sleep Apnea-Induced Cardiac Injury: Novel Insights Into Pathogenesis

Abstract

Circular RNAs (circRNAs) participate in the development of various kinds of diseases. However, the function and roles of circRNAs in obstructive sleep apnea (OSA)-induced cardiovascular disease remain poorly understood. Therefore, we sought to explore the circRNA expression profiles and predict their functions in OSA-induced cardiac injury with the use of bioinformatics analysis. The model of OSA was established in mouse treated by chronic intermittent hypoxia (CIH) exposure. Then, we screened the circRNA profile using circRNA microarray. By comparing circRNA expression in three matched pairs of CIH-treated cardiac tissues and controls, differentially expressed circRNAs were identified in the CIH groups. Comparison of the selected circRNAs expression levels was performed between qRT-PCR and microarray. Meanwhile, we employed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to predict the functions of these selected circRNAs. Finally, we constructed a circRNA-miRNA-mRNA network based on the target prediction. It was found that a total of 124 circRNAs were differentially expressed in CIH-treated cardiac tissues (p ≤ 0.05, fold-change ≥ 1.5). Among them, 23 circRNAs were significantly down-regulated, and the other 101 were up-regulated. Then, ten circRNAs were randomly selected to validate the reliability of the microarray results by using qRT-PCR. Next, we conducted the GO and KEGG pathway analysis to explore the parental genes functions of differentially expressed circRNA. Finally, two significantly differentially expressed circRNAs (mmu_circRNA_014309 and mmu_circRNA_21856) were further selected to create a circRNA-miRNA-mRNA regulation network. Our study did first reveal that the differentially expressed circRNAs played a vital role in the pathogenesis of OSA-induced cardiac damage. Thus, our findings bring us closer to unraveling the pathophysiologic mechanisms and eliciting novel therapeutic targets for the treatment of OSA-associated cardiovascular diseases.

Identification and characterization of circular RNAs expression profiles in obstructive sleep apnea-induced liver injury

“…An CIH model was established by chronic intermittent hypoxia (IH) as previously described by us [ 3 , 10 ]. Briefly, we used the intermittent hypoxia system to create a CIH environment.…”

“…OSA is a common condition with major cardiovascular consequences. At present, a great deal is known about the role of OSA in cardiovascular diseases such as myocardial infraction [ 2 ] and cardiac injury [ 3 ]. Previous studies show that severe OSA is a risk factor for abnormal liver enzymes and steatohepatitis independent of overweight states [ 4 ].…”

Comprehensive analysis of differentially expressed miRNAs in mice with kidney injury induced by chronic intermittent hypoxia

“…The mice were randomly divided into two groups: the CIH group and the control group. The CIH mouse model was established as described in our previous study ( Lai et al, 2021 ). In brief, the mice were placed in cages with a gas control system, which regulated nitrogen, air, and oxygen flow into the chambers.…”

Joint detection of miR‐149‐3p and hepcidin predicts the onset of obstructive sleep apnea syndrome in obese patients

“…However, it is reported that the occurrence of OSAS is not only induced by simple airway obstruction, but also associated with upper airway collapse and disorders in respiratory central nervous regulatory factor. 4 Activation of systemic inflammation is considered as one of the major mechanisms in the pathogenesis of OSAS, and increased inflammatory cytokines are observed in OSAS progression. 5 It is noticed that obesity is also closely related with the presence of OSAS, and about 70% OSAS patients had obesity.…”

“…The direct pathogenesis of OSAS is the stenosis and obstruction of the upper airway. However, it is reported that the occurrence of OSAS is not only induced by simple airway obstruction, but also associated with upper airway collapse and disorders in respiratory central nervous regulatory factor 4 . Activation of systemic inflammation is considered as one of the major mechanisms in the pathogenesis of OSAS, and increased inflammatory cytokines are observed in OSAS progression 5 .…”