Abstract 13856: Circulating microRNA Differentiates HFpEF and HFrEF Patients
Introduction: Circulating microRNAs (miRNAs) might reflect altered regulation of key pathways that determine the progression of heart failure (HF) and therefore provide therapeutic targets. We explored the feasibility of serum miRNA profiling in patients with HF and whether miRNA profiles are different in i) non-HF control vs. HF and ii) HF with preserved ejection fraction (HFpEF) vs HF with reduced ejection fraction (HFrEF).
Methods: Serum samples from 124 subjects were obtained from non-HF controls (n=61), patients with HFpEF (n=51), and patients with HFrEF (n=12). miRNAs were isolated, and levels of 84 miRNAs known to exhibit altered expression in cardiovascular disease were assessed using real-time quantitative PCR. Data analyses were carried out using R limma package. Multiple testing was adjusted by Benjamini-Hochberg’s approach.
Results: 57 out of 84 miRNAs had detectable expression in the serum (Ct mean<35), in which 3 miRNAs (miR-122, miR-142, and miR-143) differed significantly between HF and control subjects (adjusted p-value<0.01, absolute fold change >2). These miRNAs negatively regulate expression of pathogenic genes in cardiovascular diseases. Specifically, miR-142 targets acetyltransferase p300 and gp130, key regulators of growth and STAT3-mediated survival signals. miR-143, together with miR-145 (adjusted p-value=0.1, absolute fold change=1.9) are highly expressed in vascular smooth muscle cells (VSMCs). They are required for the transition from proliferative to contractile VSMCs via targeting known repressor genes of the contractile VSMC phenotype such as KLF4, KLF5, and ACE. One miRNA, miR-140 differed between HFpEF and HFrEF (non-adjusted p=0.03, absolute fold change>3). miR-140 targets SUMRF1, an E3 ligase for bone morphogenetic protein receptor II (BMPR2). Mutations of BMPR2 cause pulmonary arterial hypertension and cardiomyopathy in human.
Conclusions: Circulating miRNA profiles exhibit distinct patterns in control and HF that are plausibly associated with specific pathogenetic pathways in HF which may be useful biomarkers or therapeutic targets.
Author Disclosures: M. Lu: Employment; Significant; Amgen. X. Hu: Employment; Significant; Amgen. J.G. Cleland: Other Research Support; Significant; Amgen. Consultant/Advisory Board; Modest; Amgen. R. Nicholls: None. A.L. Clark: Other Research Support; Significant; Amgen. A. Khakoo: Employment; Significant; Amgen. F. Dan: Employment; Significant; Amgen. X. Wang: Employment; Significant; Amgen.
- © 2016 by American Heart Association, Inc.