Absent MicroRNAs in Different Tissues of Patients with Acquired Cardiomyopathy

Christine S Siegismund,Maria Rohde,Uwe Kühl,Felicitas Escher,Heinz Peter Schultheiss,Dirk Lassner

doi:10.1016/j.gpb.2016.04.005

Abstract

MicroRNAs (miRNAs) can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples (tissue, serum, peripheral blood mononuclear cells or other body fluids) differ significantly even in the same patient and therefore have their own specificity for the presented condition. Complex profiles of deregulated miRNAs are of high interest, whereas the importance of non-expressed miRNAs was ignored. Since miRNAs regulate gene expression rather negatively, absent miRNAs could indicate genes with unaltered expression that therefore are normally expressed in specific compartments or under specific disease situations. For the first time, non-detectable miRNAs in different tissues and body fluids from patients with different diseases (cardiomyopathies, Alzheimer’s disease, bladder cancer, and ocular cancer) were analyzed and compared in this study. miRNA expression data were generated by microarray or TaqMan PCR-based platforms. Lists of absent miRNAs of primarily cardiac patients (myocardium, blood cells, and serum) were clustered and analyzed for potentially involved pathways using two prediction platforms, i.e., miRNA enrichment analysis and annotation tool (miEAA) and DIANA miRPath. Extensive search in biomedical publication databases for the relevance of non-expressed miRNAs in predicted pathways revealed no evidence for their involvement in heart-related pathways as indicated by software tools, confirming proposed approach.

Highlights

Cardiovascular diseases as life-threatening diseases are the most common cause of death in Western European countries [1]
Improvements in human genetic studies and the continuously-expanding field of biomarker discovery revealed the potential of physiological biomarkers such as microRNAs or gene expression profiles for diagnosis of complex diseases such as cardiomyopathies and for applications in personalized medicine [9,10,11,12,13,14]. miRNA profiling can serve as a new exciting tool in modern diagnostics, which is comparable to gene expression analysis but with less amount of analytes
We focused on the non-detectable miRNAs measured on different platforms in myocardial tissue, blood cells, and serum in a large cohort of cardiac patients suffering from different forms of inflammatory or virally-induced heart muscle diseases [1,2,3,4,5]

Summary

Introduction

Cardiovascular diseases as life-threatening diseases are the most common cause of death in Western European countries [1]. Differential miRNA patterns allow the identification of different heart disorders or disease situations [17,21] The role of these human miRNAs in pathogenesis [18] highlights their value as potential molecular biomarkers for complex diseases such as cardiomyopathies [16,27,28]. We focused on the non-detectable miRNAs measured on different platforms in myocardial tissue, blood cells, and serum in a large cohort of cardiac patients suffering from different forms of inflammatory or virally-induced heart muscle diseases [1,2,3,4,5]. Experimental findings for cardiac patients were confirmed by comparisons of absent miRNAs in large cohorts of patients with different diseases [22,24,25] measured on the same analytical platforms

Results

Discussion

Material and methods