Circulating miR-4763-3p and miR-4281 are Biomarkers for Human Adult Fulminant Myocarditis

Background: Circulating miRNAs have been reported as potential biomarkers in various cardiovascular diseases. However, whether they could serve as biomarkers for human adult fulminant myocarditis (FM) is unknown. Methods: First, circulating miRNA expression profiles were detected by microarray analysis in patients with FM and healthy controls. Then, qPCR arrays were performed to validate the potential miRNAs. Meanwhile, KEGG pathway analysis was used to determine the critical roles of these circulating miRNAs in FM. Moreover, correlation analysis was employed between miRNAs and the parameters of cardiac functions in FM. Finally, the sensitivity and specificity of circulating lncRNA expression in FM diagnosis were evaluated using receiver operating characteristic curve analysis. Results: Both miRNA microarray and qPCR analysis showed that the expression of miR-4763-3p and miR-4281 were up-regulated in the plasm of FM at the onset, and their levels were restored as the clinical symptom recovered. The predicted target genes of miR-4763-3p and miR-4281 are involved in several pathways, mainly inflammatory and cardiac injury response. Moreover, the miRNAs enrichment was negatively correlated with the severity of FM. In addition, circulating miR-4763-3p and miR-4281 showed high sensitivity and specificity for FM diagnosis (AUC=0.86 and 0.78, respectively). Conclusion: This study provides global profile of circulating miRNAs in patients with FM, among which miR-4763-3p and miR-4281 could serve as potential biomarkers for FM. Trial Registration: (https://register.clinicaltrials.gov. Unique identifier: NCT03268642). Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (81822002 and 31771264 to CC, 91839302, 81630010, and 81790624 to DWW) and Tongji Hospital Clinical Research Flagship Program (2019CR207 to DWW). Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: This study was approved by the Ethics Review Board of Tongji Hospital and Tongji Medical College and conformed to the principles of the Declaration of Helsinki. Inform consents were signed by the subjects recruited in the study or by family members in case of incapacity.