Department of Forensic Genetics and Biology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, P.R. China.
Department of Forensic Pathology, School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, P.R. China.
Sci Rep. 2021 Feb 25;11(1):4695. doi: 10.1038/s41598-021-84056-5.
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.
由急性缺血性心脏病 (IHD) 引起的心脏性猝死 (SCD) 是全球范围内导致猝死的主要原因。环状 RNA (circRNA) 在心脏中大量存在，在心血管疾病中发挥重要作用，但 circRNA 作为急性 IHD 引起的 SCD 法医诊断生物标志物的作用仍未得到充分描述。为了研究两种丰富于心的 circRNA（circNFIX 和 circSLC8A1）的潜在作用，我们探索了这两种 circRNA 在不同常用 IHD 模型中的表达情况，并进一步验证了它们在法医尸检案例中的表达。来自 IHD 大鼠和 H9c2 细胞模型的结果表明，circSlc8a1 水平上调，而 circNfix 水平在缺血的早期阶段升高，随后下调。这两种 circRNA 的时间依赖性表达模式表明它们有作为 SCD 生物标志物的潜力。在尸检案例中，结果表明，在与急性 IHD 相关的 SCD 的心肌中，这两种 circRNA 的表达与缺血模型中的观察结果相对应。与心肌缺血相关的进一步分析表明，circSLC8A1 对心肌梗死具有高灵敏度和特异性，并且与心包液中的肌酸激酶 MB 呈正相关。下调的 circNFIX 水平可能表明缺血性心肌损伤，并且与冠状动脉狭窄程度呈负相关。circSLC8A1 和 circNFIX 的组合具有更好的性能来区分与 IHD 相关的 SCD。结果表明，circSLC8A1 和 circNFIX 可作为法医急性 IHD 相关 SCD 的辅助诊断标志物。
