Decreased Expression of miR-133a but Not of miR-1 is Associated with Signs of Heart Failure in Patients Undergoing Coronary Bypass Surgery

Abstract

OBJECTIVES: Coronary artery disease (CAD)-associated ischemic heart failure is characterized by dysregulated gene expression which is partly mediated by microRNAs (miRNAs). While the muscle-specific miR-1 and miR-133 are involved in cardiac development and hypertrophy, their role in heart failure resulting from CAD is unknown. We, therefore, tested the hypothesis that cardiac miR-1 and miR-133 expression is associated with signs of heart failure in patients undergoing coronary artery bypass grafting. METHODS: 83 patients were included in this prospective study. Cardiac index and vascular pressures were measured under general anesthesia and the miRNA expression was quantified (RNase protection assay and real-time PCR) from samples of the right atrial myocardium. RESULTS: miR-133 expression decreased significantly with increased severity of heart failure, as indicated by a greater New York Heart Association (NYHA) functional class (p = 0.014) and increased pulmonary artery occlusion pressure (p = 0.045). Furthermore, patients with NT-proBNP concentrations >1,800 pg/ml showed a 25% decrease in miR-133 expression compared to patients with concentrations <300 pg/ml (p = 0.023). In contrast, no associations were detected for miR-1 expression. CONCLUSIONS: In surgical CAD patients, a decreased miR-133 expression is associated with variables characteristic of heart failure. This supports a role for miR-133 but not miR-1 in the adaption to and/or remodeling of the ischemic heart.