miRNA-548c: A specific signature in circulating PBMCs from dilated cardiomyopathy patients

Abstract

High fidelity genome-wide expression analysis has strengthened the idea that microRNA (miRNA) signatures in peripheral blood mononuclear cells (PBMCs) can be potentially used to predict the pathology when anatomical samples are inaccessible like heart. PBMCs from 48 non-failing controls and 44 patients with relatively stable chronic heart failure (ejection fraction of ≤ 40%) associated with dilated cardiomyopathy (DCM) were used for miRNA analysis. Genome-wide miRNA-microarray on PBMCs from chronic heart failure patients identified miRNA signature uniquely characterized by the downregulation of miRNA-548 family members. We have also independently validated downregulation of miRNA-548 family members (miRNA-548c & 548i) using real time-PCR in a large cohort of independent patient samples. Independent in silico Ingenuity Pathway Analysis (IPA) of miRNA-548 targets shows unique enrichment of signaling molecules and pathways associated with cardiovascular disease and hypertrophy. Consistent with specificity of miRNA changes with pathology, PBMCs from breast cancer patients showed no alterations in miRNA-548c expression compared to healthy controls. These studies suggest that miRNA-548 family signature in PBMCs can therefore be used as to detect early heart failure. Our studies show that cognate networking of predicted miRNA-548 targets in heart failure can be used as a powerful ancillary tool to predict the ongoing pathology.

Serum Exosomal MiR-92b-5p as a Potential Biomarker for Acute Heart Failure Caused by Dilated Cardiomyopathy

“…In addition, miRNAs have been extensively reported as biomarkers in many human CVDs, including DCM. For example, Gupta et al demonstrated that the levels of miR-548 family members (miR-548c and miR-548i) in peripheral blood mononuclear cells were decreased in 44 patients with relatively stable chronic HF (CHF) compared with 48 non-failing controls [12]. In another study, miR-21 was found to be increased in patients with DCM, while miR-29 (miR-29a/29b/29c) and miR-133 (miR-133a/133b/133c) family members were decreased [13].…”

Down-regulation of microRNA-451a facilitates the activation and proliferation of CD4+ T cells by targeting Myc in patients with dilated cardiomyopathy

“…Apart from a direct role in the heart, miRNAs seem to be altered and to regulate gene expression in other tissues or organs, serving as another mechanism to participate in DCM. The levels of miRNA-548c were reduced in circulating peripheral blood mononuclear cells (PBMCs) from DCM patients and could be used as a reliable biomarker to predict cardiac dysfunction (19). The plasma concentration of miR-423-5p was elevated and was positively correlated with the level of N-terminal brain natriuretic peptide, thus serving as a diagnostic biomarker for heart failure caused by DCM (20).…”

miR-570 interacts with mitochondrial ATPase subunit g (ATP5L) encoding mRNA in stored platelets

“…Downregulation of miR-548 family members has been reported earlier in dilated cardiomyopathy patients, and miR-548c was identified as a potential marker for the dilated cardiomyopathy patients [21]. …”