The potential role of plasma miR‐155 and miR‐206 as circulatory biomarkers in inflammatory cardiomyopathy

Abstract

Aims Establishing a diagnosis of inflammatory cardiomyopathy (iCMP) by non-invasive means remains challenging despite advances in cardiac magnetic resonance imaging. Previous studies suggested the involvement of microRNAs in the pathogenesis of iCMP. We examined the association of a predefined set of circulatory microRNAs with clinical characteristics of iCMP and evaluated their diagnostic performance in suspected iCMP. Methods and results Eighty-nine patients with clinical suspicion of iCMP were included in the analysis. All patients underwent cardiac catheterization with left ventricular endomyocardial biopsy, echocardiography, and cardiac magnetic resonance imaging applying the Lake Louise criteria (LLC). Plasma levels of miR-21, miR-126, miR-133a, miR-146b, miR-155, and miR-206 were determined using real-time polymerase chain reaction. Based on immunohistological findings on endomyocardial biopsy, iCMP was diagnosed in 67% of study participants (n = 60). Plasma levels of miR-155 and miR-206 were significantly increased in patients with iCMP as compared with patients with dilated cardiomyopathy (P = 0.008 and P = 0.009, respectively). In receiver operating characteristic curve analysis, miR-155 and miR-206 demonstrated superior diagnostic performance for iCMP (0.68 and 0.67, respectively) compared with LLC [area under the curve (AUC) 0.60], Troponin T (AUC 0.51), and N-terminal pro-brain natriuretic peptide (AUC 0.51). While baseline miR-155 and miR-206 plasma levels were predictive for biopsy-proven iCMP (odds ratio = 2.61, 95% confidence interval = 1.28-5.31, P = 0.008 and odds ratio = 2.65, 95% confidence interval = 1.27-5.52, P = 0.009) on univariate logistic regression analysis, the presence of positive LLC, high baseline C-reactive protein, or presence of clinical symptoms and signs of viral infection failed to predict iCMP (P > 0.05, respectively). Conclusions The present data suggest that plasma levels of miR-206 and miR-155 are potential novel biomarkers for confirming the diagnosis of iCMP.

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

“…Evidence : MiR-155 level was measured in 13 studies [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Its overexpression was found mainly in MCI (5 studies) [ 10 , 13 , 14 , 19 , 21 ] and InfDCM (3 studies) [ 12 , 18 , 20 ]. Only one study identified increased expression of miR-155 in ischemic cardiomyopathy [ 20 ].…”

“…Only one study identified increased expression of miR-155 in ischemic cardiomyopathy [ 20 ]. The remaining studies did not detect increased miR-155 expression in other myocardial diseases (non-inflammatory DCM [ 11 , 12 , 17 , 18 , 19 ], rheumatic carditis [ 15 ], or hypertrophic cardiomyopathy [ 20 ]). Two studies performed ROC-AUC analysis, one for distinguishing between MCI and healthy subjects (AUC = 0.901) [ 13 ], and one for InfDCM and healthy subjects (AUC = 0.68) [ 12 ].…”

“…The remaining studies did not detect increased miR-155 expression in other myocardial diseases (non-inflammatory DCM [ 11 , 12 , 17 , 18 , 19 ], rheumatic carditis [ 15 ], or hypertrophic cardiomyopathy [ 20 ]). Two studies performed ROC-AUC analysis, one for distinguishing between MCI and healthy subjects (AUC = 0.901) [ 13 ], and one for InfDCM and healthy subjects (AUC = 0.68) [ 12 ]. One study proved the ability of the levels of miR-155 to differentiate between Coxsackie Virus B3 positive and negative DCM [ 21 ].…”

“…One study proved the ability of the levels of miR-155 to differentiate between Coxsackie Virus B3 positive and negative DCM [ 21 ]. Additionally, studies where MiR-155 expression was increased, exhibited homogeneity in the results between different types of samples: plasma [ 10 , 12 ], serum exosomes [ 13 ] and biopsy samples [ 14 , 18 , 19 , 21 ]. One study did not identify statistically significant differences between miR-155 expression in viral myocarditis and healthy subjects [ 22 ].…”

Exosomal microRNAs in diabetic heart disease

“…This encapsulation prevents miRNA degradation, increasing their stability in the circulation, allowing miRNAs to have various paracrine effects [ 29 , 94 ]. Further, this stability also allows miRNAs to function as biomarkers for various conditions [ 50 , 95 , 96 ].…”