miR-1, miR-499 and miR-208 are sensitive markers to diagnose sudden death due to early acute myocardial infarction.

ABSTRACT

MicroRNAs (miRNAs) are strongly up-regulated under pathological stress and in a wide range of diseases. In recent years, miRNAs are under investigation for their potential use as biomarkers in cardiovascular diseases. We investigate whether specific cardio-miRNAs are overexpressed in heart samples from subjects deceased for acute myocardial infarction (AMI) or sudden cardiac death (SCD), and whether miRNA could help differentiate between them. Forty four cases of death due to cardiovascular disease were selected, respectively, 19 cases categorized as AMI and 25 as SCD. Eighteen cases of traumatic death without pathological cardiac involvement were selected as control. Immunohistochemical investigation was performed for CD15, IL-15, Cx43, MCP-1, tryptase, troponin C and troponin I. Reverse transcription and quantitative real-time PCR were performed for miR-1, miR-133, miR-208 and miR-499. In AMI group, stronger immunoreaction for the CD15, IL-15 and MCP-1 antibodies was detectable compared with SCD and control. Cx43 showed a negative reaction with respect to the other groups. Real-time PCR results showed a down-regulation of all miRNAs in the AMI group compared with SCD and control. The selected miRNAs presented high accuracy in discriminating SCD from AMI (miR-1 and miR-499) and AMI from control (miR-208) representing a potential aid for both clinicians and pathologists for differential diagnosis.