Abstract 610: Microrna-146a Accumulates in the Atherosclerotic Plaque but Decreases in Circulation of Patients With ST Segment Elevation MI

MicroRNAs (miRNAs) function as regulators of gene expression intracellularly or as paracrine signals extracellularly. Their role in modulation of cardiovascular disease is emerging. Changes in miRNA profiles have been characterized in the circulation of patients with myocardial infarction (MI), but little is known of the correlation between circulating and plaque miRNAs during atherosclerosis progression and ST-elevated MI (STEMI). During percutaneous interventions (PCI), angioplasty catheter balloons can retain plaque debris post-inflation and may provide insight into plaque miRNA expression in disease. Our objective was to assess the correlation between miRNA levels in circulation and plaques of patients with coronary artery disease (CAD), including those with ST segment elevation MI (STEMI). We collected balloons and plasma from patients undergoing PCI for STEMI (n=6) or elective cardiac catheterization (n=2). Plasma was collected from age and sex-matched patients at low risk for CAD (n=5) or with stable CAD (n=6). RNA was extracted from balloon-adherent debris and patient plasma and sequenced. miRNA levels were validated by qRT-PCR. Deep sequencing of patient plasma suggested a decrease in levels of circulating miR-146a-5p in STEMI patients (fig A). This miRNA is found in several cell types (endothelial cells, immune cells, and macrophages), and targets inflammatory signaling pathways. Via PCR, we found that levels of circulating miR-146a dropped markedly both in patients with stable CAD and STEMI (fig B). However, the trend was reversed in plaques; miR-146a levels increased 15-fold from stable to ruptured plaques (fig C). We postulate that miR-146a accumulation in plaques is a compensatory response to inflammation, but that the drop in circulating miR-146a levels may contribute to atherosclerotic plaque instability. These findings have implications for development of miRNA-based strategies for diagnosis and management of vulnerable plaques.