Although several risk factors such as
infarct size have been identified, the progression of
heart failure (HF) remains difficult to predict in clinical practice. Using an experimental rat model of post-
myocardial infarction (MI), we previously identified 45
proteins differentially modulated during HF by proteomic analysis. This study sought to identify
microRNAs (
miRNAs) able to regulate these
proteins and to test their relevance as
biomarkers for HF. In silico bioinformatical analysis selected 13
miRNAs related to the 45
proteins previously identified. These
miRNAs were analyzed in the rat and in cohorts of patients phenotyped for
left ventricular remodeling (LVR). We identified that 3
miRNAs, miR-21-5p, miR-23a-3p and miR-222-3p, and their target
Mn superoxide dismutase (SOD2) were significantly increased in LV and plasma of HF-rats. We found by
luciferase activity a direct interaction of miR-222-3p with
3'UTR of SOD2. Transfection of human cardiomyocytes with miR-222-3p mimic or inhibitor induced respectively a decrease and an increase of SOD2 expression. Circulating levels of the 3
miRNAs and their target SOD2 were associated with high LVR post-MI in REVE-2 patients. We demonstrated for the first time the potential of
microRNAs regulating SOD2 as new circulating
biomarkers of HF.