Identification of cardiac-related serum miRNA in patients with type 2 diabetes mellitus and heart failure: Preliminary report

Abstract

Diabetic patients present an increased risk for heart failure (HF) independently of the presence of coronary artery disease (CAD) and hypertension. However, little is known about circulatory microRNA (miRNA), an important regulatory RNA in this population. To evaluate serum miRNA profile of patients with diabetes mellitus (DM) and HF and analyze its relationship with pathophysiological pathways involved. The accumulation of 179 miRNAs was measured in serum of diabetic patients with HF and compared to the same measurements in healthy control subjects. The miRNAs were assayed using quantitative polymerase chain reaction (qPCR) on the Serum/Plasma Focus microRNA PCR panel (Qiagen) with LightCycler® 96 Real-Time PCR System (Roche). A pairwise comparison of mean relative miRNA accumulation levels was performed to establish those miRNAs that are differently expressed in patients with: 1) HF; 2) HF and chronic coronary syndrome (HF-CAD); and 3) HF without chronic coronary syndrome (HF-nonCAD) compared to healthy controls. To gain insight into these functions of miRNAs, we applied Gene Ontology (GO) enrichment analysis of Biological Processes and Molecular Functions of their predicted targets. The pairwise comparison revealed that 12 miRNAs were significantly downregulated in HF-CAD patients compared to controls, whereas 4 miRNAs were considerably deregulated in HF-nonCAD patients, with miRNA-15b-5p being downregulated in both groups. The GO analysis revealed that differentially accumulated targets of miRNAs include genes involved in potassium channel function, MAPK kinase activity and DNA transcription regulation, with similar alterations observed in the whole HF group and HF-CAD subgroup as well as a response to stress and apoptosis (in HF group), and genes involved in the development (in HF-CAD group). No oriented specialization of deregulated miRNA targets was observed in the HF-nonCAD subgroup. We observed a significant downregulation of 13 miRNAs in diabetic HF patients, which was not reported previously either in HF or diabetic patients. Downregulated miRNAs regulate angiogenesis and apoptosis.