Abstract P1109: Investigating The Role Of Human Conserved Microrna-193 In The Aging Drosophila Heart

MicroRNAs (miRNAs) are short, non-coding, RNAs that post-transcriptionally regulate gene expression and are ideal candidates for the regulation of the genes responsible in the heart. Profiling studies have shown circulating miRNAs to be implicated in human cardiovascular disease with the potential to be used as biomarkers for various cardiovascular pathologies. Highly conserved with Drosophila miR-193, human miR-193 is expressed in the heart and has been established as a biomarker to distinguish between patients with different types of heart failure, including HFPEF, hypertrophic cardiomyopathy, ischemia reperfusion injury, right ventricular remodeling, cardiac fibrosis, and congenital heart disease. However, without the mechanism and regulation of its target genes, the use of miR-193 as a biomarker or therapeutic is limited. We have characterized the impact of miR-193 loss on homoeostasis of heart morphology and function in drosophila during aging using a combination of null mutants and heart specific dysregulation of miR-193 expression. Using SOHA (semi-automated optical heartbeat analysis), we observed changes occurring to heart structure and function with a loss of miR-193. With miR-193 dysregulation, significant changes in heart rate, heart size (diastolic and systolic diameters), arrhythmia index, and diastolic/relaxation interval time, began at 10 days post-eclosion and continued as the flies aged. Understanding the role of miRNAs in specific tissues and disease states will ultimately depend on our ability to dissect the fundamental strategies and mechanisms by which miRNAs regulate cardiac biology. Using in silico analysis, we have identified multiple human conserved putative miRNA-target gene interactions to further characterize the molecular mechanisms underlying the observed phenotypes. Our results suggest that the human conserved Drosophila miR-193 is essential for normal cardiac function. In miR-193 loss of function, we see significant changes to heart rate, heart size, and interval time consistent with an early aging phenotype. The conservation of miR-193 and its predicted gene targets enable us to discover the molecular mechanisms that underlie miRNA dysregulation in cardiovascular disease.