MicroRNA profiling of the feline left heart identifies chamber-specific expression signatures in health and in advanced hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a common heart disease in humans and cats, nonetheless, the disease pathogenesis is still poorly understood. MicroRNAs are suspected to be involved in the disease process but the myocardial microRNA expression pattern in cats has not been identified. We hypothesized that microRNA profiles differ between healthy cats and cats with HCM. Small RNA sequencing on left ventricle (LV) and left atria (LA) samples from healthy cats (8 LV, 8 LA) and cats with HCM (7 LV, 5 LA) was performed. We identified 1039 differentially expressed microRNAs (False Discovery Rate <0.01, fold change >2). Cats with HCM were found to have a distinct microRNA expression profile with apparent regional heterogeneity. Comparing the HCM and control hearts, we detected 80 differentially expressed microRNAs for the HCM LV, and 37 for the LA. These included LV and LA enriched miR-21, miR-146b, and reduced miR-122-5p, which were recently suggested as key microRNAs for the HCM pathogenesis, and miR-132, which might be of therapeutic interest. Several top enriched microRNAs: miR-3958, miR-382-5p, miR-487a-5p (HCM LV); miR-chrD4_30107-3p (HCM LA); miR-3548 (HCM LV and LA) have either not been reported in the heart or only little is known. We identified potentially relevant microRNAs and further investigations into their role are required. Genes known to be targeted by the differentially expressed microRNAs were associated with inflammation and growth pathways in the HCM LV and LA, cardioprotective pathways in the LV, and fibrosis and structural changes in the LA when compared to healthy hearts.