Impact of chronic intermittent hypoxia on the long non-coding RNA and mRNA expression profiles in myocardial infarction.

Chaowei Hu,Yunhui Du,Yanwen Qin,Yongxiang Wei,Yifan Jia,Yunyun Yang,Jing Li,Lu Peng,Juan Li

doi:10.1111/jcmm.16097

Abstract

Chronic intermittent hypoxia (CIH) is the primary feature of obstructive sleep apnoea (OSA), a crucial risk factor for cardiovascular diseases. Long non‐coding RNAs (lncRNAs) in myocardial infarction (MI) pathogenesis have drawn considerable attention. However, whether CIH participates in the modulation of lncRNA profiles during MI is yet unclear. To investigate the influence of CIH on MI, cardiac damage was assessed by histology and echocardiography, and lncRNA and mRNA integrated microarrays were screened. MI mouse model showed myocardial hypertrophy, aggravated inflammation and fibrosis, and compromised left ventricle function under CIH. Compared with normoxia, 644 lncRNAs and 1084 differentially expressed mRNAs were identified following CIH for 4 weeks, whereas 1482 lncRNAs and 990 mRNAs were altered at 8 weeks. Strikingly, reoxygenation after CIH markedly affected 1759 lncRNAs and 778 mRNAs. Of these, 11 lncRNAs modulated by CIH were restored after reoxygenation and were validated by qPCR. The GO terms and KEGG pathways of genes varied significantly by CIH. lncRNA‐mRNA correlation further showed that lncRNAs, NONMMUT032513 and NONMMUT074571 were positively correlated with ZEB1 and negatively correlated with Cmbl. The current results demonstrated a causal correlation between CIH and lncRNA alternations during MI, suggesting that lncRNAs might be responsible for MI aggravation under CIH.

Highlights

It was observed that compared with normoxia, Chronic intermittent hypoxia (CIH) was conducive to high mRNA and protein expression of HIF-1α in the infarcted heart (Figure S1D,E). These findings demonstrated that exposure to CIH worsens the heart injury post-myocardial infarction (MI)
For the core Long non-coding RNAs (lncRNAs) NONMMUT032513 and NONMMUT074571, we observed that lncRNA NONMMUT032513 is positively linked with zinc finger E-box binding homeobox 1 (ZEB1) and smad[5], lncRNA NONMMUT074571 is positively correlated with ZEB1 and Smtn, lncRNA NONMMUT032513 is negatively associated with Cmbl and ADH5, and lncRNA NONMMUT074571 is negatively correlated with Cmbl and Pfdn[6] (Figure 5A)
The cAMP signalling pathway and NONMMUT032513 and NONMMUT074571 lncRNAs are indicated as the putative players most likely to contribute to heart injury under CIH conditions

Summary

| INTRODUCTION

Myocardial infarction (MI) results from acute coronary artery stenosis and occlusion and is often complicated with arrhythmia and heart failure, leading to high mortality.[1]. Obstructive sleep apnoea (OSA) is a common sleep disorder in the adult population and is associated with various cardiovascular diseases. It has been recognized as an independent risk factor for hypertension, arrhythmia and heart failure, among other conditions.[4,5]. Some studies suggested that lncRNAs display various biological functions[12] that include indirect regulation of gene expression. These phenomena affect cellular processes via post-transcriptional regulation and nuclear transport.[13,14]. The present study aimed to confirm the causal correlation between CIH and cardiac damage after MI and explore the lncRNA expression profiles

| MATERIALS AND METHODS

Findings

| DISCUSSION