A Systematic Review of miRNA and cfDNA as Potential Biomarkers for Liquid Biopsy in Myocarditis and Inflammatory Dilated Cardiomyopathy

Abstract

Myocarditis and inflammatory dilated cardiomyopathy are cardiac diseases leading to heart failure. Liquid biopsy is a concept of replacing traditional biopsy with specialized blood tests. The study aim was to summarize and assess the usefulness of microRNAs and circulating free DNA as biomarkers of myocardial inflammation. For this systematic review, we searched Scopus, Embase, Web of Science, and PubMed. All studies measuring microRNAs in serum/plasma/cardiac tissue or circulating free DNA during myocarditis and non-ischemic dilated cardiomyopathy in humans in which healthy subjects or another cardiac disease served as a comparator were included. Data were extracted and miRNAs were screened and assessed using a scale created in-house. Then, highly graded miRNAs were assessed for usability as liquid biopsy biomarkers. Of 1185 records identified, 56 were eligible and 187 miRNAs were found. We did not identify any studies measuring circulating free DNA. In total, 24 of the screened miRNAs were included in the final assessment, 3 of which were selected as the best and 3 as potential candidates. We were not able to assess the risk of bias and the final inclusion decision was made by consensus. Serum levels of three miRNAs—miR-Chr8:96, miR-155, and miR-206—are the best candidates for myocardial inflammation liquid biopsy panel. Further studies are necessary to prove their role, specificity, and sensitivity.

MicroRNAs as novel biomarkers and potential therapeutic options for inflammatory cardiomyopathy

“…MicroRNA‐1 (miR‐1) is a conserved miRNA with high expression in muscle tissues (muscle‐specific miRNA), particularly in the heart muscle, which is involved in the development of this tissue 43 . MiR‐1 has been extensively investigated and confirmed as a key regulator of cardiac development and diseases 16,44 . The results of several studies further suggest that the patterns of miR‐1 expression are model and/or disease dependent, because miR‐1 plays a critical role in the physiological processes in the smooth and skeletal muscles, as well as in other tissues, and thus is involved in the pathogenesis of a variety of disorders 43 …”

“…Moreover, miR‐155 has been found to be involved in viral infections, particularly those caused by DNA viruses 53 . According to the analyses of Lewandowski et al ., miR‐155 is among the leading candidates for a myocardial inflammation panel 16 . MiR‐155 has also been shown to be involved in the impaired development and function of B cells, T cells, and dendritic cells 54 .…”

“…Therefore, new data open the possibility of developing a new area of specific drugs that will enable further development of specific causal and personalized therapy. In this context, it should be pointed out that a systematic review on the role of liquid biopsy regarding the role of miRNAs as potential biomarkers for myocarditis and DCMi already identified miRNAs, which have now also been identified in blood of DCMi patients, as the best candidates for myocardial inflammation 16 . Furthermore, it is very important to emphasize that in the here presented miRNA, a differentiation between virus‐positive and virus‐negative DCMi patients could be achieved for the first time.…”

“…Depending on the target, 14 miRNAs can either promote or suppress inflammation 15,16 . The regulation of inflammation is caused primarily through altered expression of specific miRNAs 14 .…”

“…Depending on the target, 14 miRNAs can either promote or suppress inflammation. 15 , 16 The regulation of inflammation is caused primarily through altered expression of specific miRNAs. 14 There is also evidence that the biogenesis of miRNAs is regulated as part of the inflammatory response, by altering the transcription level, processing or stabilization of mature or precursor miRNA transcripts.…”