CircSLC8A1 and circNFIX can be used as auxiliary diagnostic markers for sudden cardiac death caused by acute ischemic heart disease

Meihui Tian,Jiajia Xue,Hao Pang,Enzhu Jiang,Cuiyun Dai,Baoli Zhu

doi:10.1038/s41598-021-84056-5

Meihui Tian, Jiajia Xue + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-84056-5

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Journal: Scientific Reports	Publication Date: Feb 25, 2021
Citations: 19	License type: open-access

Affiliation: China Medical University

Abstract

Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide. Circular RNAs (circRNAs) are abundant in the heart and play important roles in cardiovascular diseases, but the role of circRNAs as biomarkers in the forensic diagnosis of SCD caused by acute IHD remains poorly characterized. To investigate the potential of two heart-enriched circRNAs, circNFIX and circSLC8A1, we explored the expression of these two circRNAs in different kinds of commonly used IHD models, and further verified their expressions in forensic autopsy cases. The results from both the IHD rat and H9c2 cell models revealed that circSlc8a1 level was upregulated, while the circNfix level was elevated in the early stage of ischemia and subsequently downregulated. The time-dependent expression patterns of the two circRNAs suggested their potential as SCD biomarkers. In autopsy cases, the results showed that the expression of these two circRNAs in the myocardium with acute IHD-related SCDs corresponded to the observations in the ischemic models. Further analysis related to myocardial ischemia indicated that circSLC8A1 showed high sensitivity and specificity for myocardial infarction and was positively correlated with creatine kinase MB in pericardial fluid. Downregulated circNFIX level could indicate the ischemic myocardial damage, and it was negatively correlated with the coronary artery stenosis grade. The combination of circSLC8A1 and circNFIX had better performance to discriminate IHD-related SCDs. The results suggested that circSLC8A1 and circNFIX may be used as auxiliary diagnostic markers for SCD caused by acute IHD in forensic medicine.

Highlights

Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide
Vausort et al found that the serum expression levels of myocardial infarction-associated circular RNA (MICRA) were lower in MI patients than in healthy volunteers and that the MICRA expression level might predict the extent of left ventricular dysfunction after MI14,20
After the injection of B aCl2 solution, the ECGs of rats immediately showed the waveforms of ventricular arrhythmia (VA)

Summary

Introduction

Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide. To investigate the potential of two heart-enriched circRNAs, circNFIX and circSLC8A1, we explored the expression of these two circRNAs in different kinds of commonly used IHD models, and further verified their expressions in forensic autopsy cases. The results from both the IHD rat and H9c2 cell models revealed that circSlc8a1 level was upregulated, while the circNfix level was elevated in the early stage of ischemia and subsequently downregulated. The purpose of this study was to explore the potential of these two circRNAs as biomarkers for IHD-related SCD diagnosis in forensic autopsy cases For this purpose, we first investigated the expression of these two circRNAs in different kinds of commonly used IHD models. We focused on verifying their expressions in forensic autopsy cases, and evaluated their application prospects in forensic medicine

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