Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias

Abstract

Background Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored. Methods Sprague-Dawley (SD) rats were randomly divided into two groups ( n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA–mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR). Results Eight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA–mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17. Conclusions Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia–RA.

Protective Role of Amiodarone on Reperfusion Arrhythmia in Patients of Acute Myocardial Infarction with Percutaneous Coronary Intervention Treatment

“…Amiodarone is a class III antiarrhythmic drug that can delay ischemic myocardial conduction and reduce the action potential of ischemic and nonischemic myocardium, thereby reducing reentrant excitation and triggered activity and helping to inhibit the occurrence of arrhythmia [ 12 ]. Clinical studies have shown that in acute myocardial ischemia or myocardial infarction, amiodarone can increase the activity of ion channels without aggravating the deterioration of cardiac function and has no effect on myocardial ischemia [ 13 , 14 ].…”

Potentially Functional microRNA-mRNA Regulatory Networks in Intestinal Ischemia-Reperfusion Injury: A Bioinformatics Analysis

“…As an inconsistent Co-DE miRNA, the expression of miR-122-5p varied in intestinal ischemia-reperfusion injury and ischemia-reperfusion induced arrhythmias. 26 MiR-27a-5p had been associated with a decreased level of Bach1 mRNA, which reduced apoptosis in liver ischemia-reperfusion injury. 27 Elsewhere, miR-1247-3p alleviated the damage of myocardial ischemia-reperfusion by targeting both BCL2L11 and caspase-2.…”

Non-coding RNA and arrhythmias: expression, function, and molecular mechanism

“…reported that eight dysregulated miRNAs are most closely associated with hypothermic ischaemia–reperfusion arrhythmia in rats, and the miRNA–mRNA interaction network suggested that novel miR-17 may target CJA1 to participate in reperfusion arrhythmias. 86 …”