MicroRNA-1 and microRNA-499 as potential time-dependent biomarkers for the detection of early myocardial ischaemia

Abstract Post-mortem diagnosis of ​ acute myocardial infarction (AMI) remains one of the major challenges in forensic pathology, as conventional macroscopic, histological and immunohistochemical techniques lack sufficient sensitivity within the first hour after onset of ischaemia. Using the established isolated-perfused rat heart model according to Langendorff, this study aimed to evaluate the feasibility and diagnostic potential of myocardial microRNA (miRNA) expression analysis for detecting very early ischaemic conditions. Myocardial expression patterns of four cardiac-enriched miRNAs (miRNA-1-3p, miRNA-133a-3p, miRNA-208a-3p and miRNA-499-5p) were investigated. After 30 min of ischaemia, distinct upregulation of miRNA-1 and miRNA-499 was observed in ischaemic myocardium. Following prolonged ischaemia of 240 min, expression levels of all four miRNAs declined in ischaemic myocardial tissue. These findings suggest an early, transient increase in selected cardiac-enriched miRNAs followed by a decrease with ongoing ischaemia, reflecting a dynamic, time-dependent regulation pattern. Our data demonstrate that myocardial miRNA alterations occur within 30 min of ischaemia. Specifically, we identified miRNA-1 and miRNA-499 as promising early indicators of acute ischemic myocardial injury. Thus, miRNA expression profiling may serve as a valuable adjunct to established forensic diagnostic approaches, particularly when survival times are short and conventional morphological methods reach their limits. Further validation in human post-mortem material is necessary to confirm the diagnostic applicability.