MicroRNAs as novel biomarkers and potential therapeutic options for inflammatory cardiomyopathy

Abstract

Aims: Inflammation of the heart is a complex biological and pathophysiological response of the immune system to a variety of injuries leading to tissue damage and heart failure. MicroRNAs (miRNAs) emerge as pivotal players in the development of numerous diseases, suggesting their potential utility as biomarkers for inflammation and as viable candidates for therapeutic interventions. The primary aim of this investigation was to pinpoint and assess particular miRNAs in individuals afflicted by virus-negative inflammatory dilated cardiomyopathy (DCMi).

Methods and results: The study involved the analysis of 152 serum samples sourced from patients diagnosed with unexplained heart failure through endomyocardial biopsy. Among these samples, 38 belonged to DCMi patients, 24 to DCM patients, 44 to patients displaying inflammation alongside diverse viral infections, and 46 to patients solely affected by viral infections without concurrent inflammation. Additionally, serum samples from 10 healthy donors were included. The expression levels of 754 distinct miRNAs were evaluated using TaqMan OpenArray. MiR-1, miR-23, miR-142-5p, miR-155, miR-193, and miR-195 exhibited exclusive down-regulation solely in DCMi patients (P < 0.005). These miRNAs enabled effective differentiation between individuals with inflammation unlinked to viruses (DCMi) and all other participant groups (P < 0.005), boasting a specificity surpassing 86%.

Conclusions: The identification of specific miRNAs offers a novel diagnostic perspective for recognizing intramyocardial inflammation within virus-negative DCMi patients. Furthermore, these miRNAs hold promise as potential candidates for tailored therapeutic strategies in the context of virus-negative DCMi.

Keywords: Biomarker; Cardiomyopathy; Inflammation; MiRNA.

Figure 1

(A–D) Immunohistochemical staining for detection of endomyocardial inflammation.

Figure 2

Confirmation of differentially expressed microRNAs (miRNAs) in patients with inflammatory dilated cardiomyopathy (DCMi). P‐values are shown in comparison of DCMi patients with other groups.

Figure 3

Diagnostic value of microRNAs (miRNAs) for inflammatory dilated cardiomyopathy presented in receiver operating characteristic (ROC) curves with area under the curve (AUC) compared with all other patients. The ROC curve illustrates the diagnostic ability of a binary classifier system when its discrimination threshold is varied. It was constructed by plotting the true positive rate (sensitivity) against the false positive rate (specificity). AUC is equal to the probability that a classifier will rank a randomly selected positive instance higher than a randomly selected negative one.