Exosomes are important mediators of intercellular communication and modulate various biological processes[1]. However, the role of exosomes in various pathological conditions and their potential involvement in disease mechanisms need to be further investigated. Cardiac hypertrophy is a pathological condition characterized by an increase in the size and mass of cardiomyocytes, leading to impaired cardiac function and increased risk of heart failure[2]. We hypothesize that hypertrophic cardiomyocytes secrete exosomes triggering the progression of cardiac hypertrophy,.
Aims: The aim of this study is to investigate the roles of exosomes in cardiac hypertrophy and the relationship between the transcriptomes of exosomes and their parent cells.
Methods: iPS-derived cardiomyocytes (hiPSC-CMs) were used in an in vitro model of cardiac hypertrophy. Exosomes were isolated from the conditioned media 24h post Endothelin-1 stimulation. RNA content of both cells and exosomes were characterized by RNA-seq and compared to the untreated control samples.
Results: Exosomes from hypertrophic hiPSC-CMs had significantly elevated levels of several hypertrophy markers, such as NPPA, NPPB, CTGF and THBS1 compared to the control hiPSC-CM. We identified 961 differentially expressed genes (DEGs) that showed significant association to many cardiac clinical outcomes, e.g. “Cardiac enlargement”. The gene expression profile showed activation of several pathways involved in cardiac hypertrophy such as ´Cardiac hypertrophy signaling´ and `Actin cytoskeleton´. 76% similarity was observed between the DEGs in exosomes and parent cells.
Conclusions: Our results suggest that exosomes are involved in the pathogenesis of cardiac hypertrophy and that exosomes may be a valid therapeutic target for potential treatments.