Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy

Maria Calderon-Dominguez,Thalía Belmonte,Juan Calderon-Dominguez,Oscar Campuzano,Mónica Ramos,Maribel Quezada-Feijoo,Alipio Mangas,Rocio Toro

doi:10.1038/s41598-021-87086-1

Abstract

The left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify high-risk patients. Thus, we investigated whether microRNA profiles can categorize DCM patients based on their EF. 179-differentially expressed circulating microRNAs were screened in two groups: (1) non-idiopathic DCM; (2) idiopathic DCM. Then, 26 microRNAs were identified and validated in the plasma of ischemic-DCM (n = 60), idiopathic-DCM (n = 55) and healthy individuals (n = 44). We identified fourteen microRNAs associated with echocardiographic variables that differentiated idiopathic DCM according to the EF degree. A predictive model of a three-microRNA (miR-130b-3p, miR-150-5p and miR-210-3p) combined with clinical variables (left bundle branch block, left ventricle end-systolic dimension, lower systolic blood pressure and smoking habit) was obtained for idiopathic DCM with a severely reduced-EF. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. Bioinformatics analysis revealed that miR-150-5p and miR-210-3p target genes might interact with each other with a high connectivity degree. In conclusion, our results revealed a three-microRNA signature combined with clinical variables that highly discriminate idiopathic DCM categorization. This is a potential novel prognostic biomarker with high clinical value.

Highlights

Department, School of Medicine, University of Cadiz, Edifício Andrés Segovia 3o Floor, C/Dr Marañón S/N, Scientific Reports | (2021) 11:7517
Dilated cardiomyopathy (DCM) is a heterogeneous heart disease characterized by the presence of left ventricular (LV) dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment[1,2]
DCM group exhibited an increase in left atrium diameter (LA) and volume, sphericity index, and E/e’ ratio, compared with the control group

Summary

Introduction

Department, School of Medicine, University of Cadiz, Edifício Andrés Segovia 3o Floor, C/Dr Marañón S/N, Scientific Reports | (2021) 11:7517. Dilated cardiomyopathy (DCM) is a heterogeneous heart disease characterized by the presence of left ventricular (LV) dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment[1,2] This entity encompasses different phenotypes, clinical features and etiologies with a common final pathway. Circulating levels of B-type natriuretic peptide or related molecules are very useful for clinical tailoring They are not highly specific, as they are not good as systolic function m arkers[4]. MicroRNAs (miRNAs) are evolutionary conserved non-coding RNA molecules of 19–25 nucleotides that play crucial roles in modulating the expression of most proteins at post-transcriptional level[9] Their properties make them the most widely studied extracellular RNAs as diagnostic, prognostic and therapeutic markers in the cardiovascular field[10,11,12]. We evaluated plasma miRNAs as potential biomarkers to discriminate severe from moderate reduced EF in a DCM population

Methods

Results

Conclusion