Biomarkers of
heart failure in adults have been extensively studied. However,
biomarkers to monitor the progression of
heart failure in children with univentricular physiology are less well understood. We proposed that as mediators of diverse pathophysiology,
miRNAs contained within circulating microvesicles could serve as
biomarkers for the presence and progression of
heart failure in univentricular patients. To test this, we studied the association of
heart failure with elevations in specific
miRNAs isolated from circulating microvesicles in a cohort of children with
univentricular heart disease and
heart failure. We conducted a single site cross-sectional observational study of 71 children aged 1 month-7 years with
univentricular heart disease and
heart failure. We demonstrated that levels of miR129-5p isolated from plasma microvesicles were inversely related to the degree of clinical
heart failure as assessed by Ross score. We then showed that miR129-5p levels are downregulated in HL1 cells and human embryonic stem cell-derived cardiomyocytes exposed to oxidative stress. We demonstrated that
bone morphogenetic protein receptor 2, which has been implicated in the development of pulmonary
vascular disease, is a target of miR129-5p, and conversely regulated in response to oxidative stress in cell culture. Levels of miR129-5p were inversely related to the degree of clinical
heart failure in patients with
univentricular heart disease. This study demonstrates that miR129-5p is a sensitive and specific
biomarker for
heart failure in
univentricular heart disease independent of ventricular morphology or stage of palliation. Further study is warranted to understand the targets affected by miR129-5p with the development of
heart failure in patients with univentricular physiology.