Multiparametric diagnostics of cardiomyopathies by microRNA signatures

AbstractThe diagnosis of cardiomyopathies by endomyocardial biopsy analysis is the gold standard for confirmation of causative reasons but is failing if a sample does not contain the area of interest due to focal pathology. Biopsies are revealing an extract of the current situation of the heart muscle only, and the need for global organ-specific or systemic markers is obvious in order to minimize sampling errors. Global markers like specific gene expression signatures in myocardial tissue may therefore reflect the focal situation or condition of the whole myocardium. Besides gene expression profiles, microRNAs (miRNAs) represent a new group of stable biomarkers that are detectable both in tissue and body fluids. Such miRNAs may serve as cardiological biomarkers to characterize inflammatory processes, to confirm viral infections, and to differentiate various forms of infection. The predictive power of single miRNAs for diagnosis of complex diseases may be further increased if several distinctly deregulated candidates are combined to form a specific miRNA signature. Diagnostic systems that generate disease-related miRNA profiles are based on microarrays, bead-based oligo sorbent assays, or on assays based on real-time polymerase chain reactions and placed on microfluidic cards or nanowell plates. Multiparametric diagnostic systems that can measure differentially expressed miRNAs may become the diagnostic tool of the future due to their predictive value with respect to clinical course, therapeutic decisions, and therapy monitoring. We discuss here specific merits, limitations and the potential of currently available analytical platforms for diagnostics of heart muscle diseases based on miRNA profiling. Contains 34 references. FigureModern diagnostics of cardiomyopathies will include multiparametric analysis of microRNA profiles in endomyocardial biopsies by real-time PCR or bead-based OLISA techniques. In contrast to high-throughput screening technologies diagnostic systems are realized by down-scaling sample volumes and simultaneous measurement of a limited number of stable disease related parameters.

[1]  Caifu Chen,et al.  Stem-loop RT-qPCR for microRNA expression profiling. , 2012, Methods in molecular biology.

[2]  Hugo A. Katus,et al.  A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction , 2013, European heart journal.

[3]  K. Kellar,et al.  Multiplexed fluorescent bead-based immunoassays for quantitation of human cytokines in serum and culture supernatants. , 2001, Cytometry.

[4]  A. Dörner,et al.  A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression , 2013, Basic Research in Cardiology.

[5]  Eugene Berezikov,et al.  A Deep Sequencing Approach to Uncover the miRNOME in the Human Heart , 2013, PloS one.

[6]  W. Ansorge.  Next-generation DNA sequencing techniques. , 2009, New biotechnology.

[7]  U. Sack,et al.  New Platform Technology for Comprehensive Serological Diagnostics of Autoimmune Diseases , 2012, Clinical & developmental immunology.

[8]  Chang-gong Liu,et al.  miRNA-548c: a specific signature in circulating PBMCs from dilated cardiomyopathy patients. , 2013, Journal of molecular and cellular cardiology.

[9]  Stephane Heymans,et al.  MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis , 2012, Circulation research.

[10]  Christina Backes,et al.  Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing , 2014, Multiple sclerosis.

[11]  Carlos Cordon-Cardo,et al.  miR-143, miR-222, and miR-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer. , 2012, The American journal of pathology.

[12]  R. Hetzer,et al.  Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies , 2008, BMC Molecular Biology.

[13]  G. Zamboni,et al.  Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients , 2013, International journal of cancer.

[14]  F. Mallet,et al.  Multiplex degenerate PCR coupled with an oligo sorbent array for human endogenous retrovirus expression profiling , 2006, Nucleic acids research.

[15]  H. Schultheiss,et al.  Viral Persistence in the Myocardium Is Associated With Progressive Cardiac Dysfunction , 2005, Circulation.

[16]  Q. Fang,et al.  Nanoliter droplet array for microRNA detection based on enzymatic stem-loop probes ligation and SYBR Green real-time PCR. , 2011, Talanta.

[17]  Thomas Thum,et al.  MicroRNAs: novel regulators in cardiac development and disease. , 2008, Cardiovascular research.

[18]  U. Laufs,et al.  Role of miR-21 in the pathogenesis of atrial fibrosis , 2012, Basic Research in Cardiology.

[19]  L. Cooper,et al.  The management of myocarditis. , 2011, European heart journal.

[20]  S. Frigstad,et al.  ASAT/ALAT ratio provides prognostic information independently of Child-Pugh class, gender and age in non-alcoholic cirrhosis , 2008, Scandinavian journal of gastroenterology.

[21]  H. Fechner,et al.  Genomic expression profiling of human inflammatory cardiomyopathy (DCMi) suggests novel therapeutic targets , 2006, Journal of Molecular Medicine.

[22]  C. Tschöpe,et al.  Improved diagnosis of idiopathic giant cell myocarditis and cardiac sarcoidosis by myocardial gene expression profiling. , 2014, European heart journal.

[23]  Manuel Mayr,et al.  MicroRNAs in vascular and metabolic disease. , 2012, Circulation research.

[24]  Tiina Heliö,et al.  Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. , 2013, European heart journal.

[25]  J. Hurley,et al.  miRNA profiling on high-throughput OpenArray™ system. , 2011, Methods in molecular biology.

[26]  H. Schultheiss,et al.  miRNA as activity markers in Parvo B19 associated heart disease , 2012, Herz.

[27]  Christine S. Siegismund,et al.  Recent Advances in Molecular Diagnostics and Treatment of Heart Muscle Diseases , 2013 .

[28]  Sek Won Kong,et al.  Altered microRNA expression in human heart disease. , 2007, Physiological genomics.

[29]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[30]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[31]  F. Crea,et al.  Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients. , 2009, Physiological genomics.

[32]  Waibhav Tembe,et al.  Identification of extracellular miRNA in human cerebrospinal fluid by next-generation sequencing. , 2013, RNA.

[33]  J. Lupski,et al.  The complete genome of an individual by massively parallel DNA sequencing , 2008, Nature.

[34]  Anne Kopf-Sill,et al.  Novel isothermal, linear nucleic acid amplification systems for highly multiplexed applications. , 2005, Clinical chemistry.

[35]  C. Tschöpe,et al.  Recent Advances in Molecular Diagnostics and Treatment of Heart Muscle Diseases , 2013 .