Abstract
Extracellular vesicles (EVs) have recently emerged as an important carrier for various genetic materials including microRNAs (miRs). Growing evidences suggested that several miRs transported by EVs were particularly involved in modulating cardiac function. However, it has remained unclear what miRs are enriched in EVs and play an important role in the pathological condition. Therefore, we established the miR expression profiles in EVs from murine normal and failing hearts and consecutively identified substantially altered miRs. In addition, we have performed bioinformatics approach to predict potential cardiac outcomes through the identification of miR targets. Conclusively, we observed approximately 63% of predicted targets were validated with previous reports. Notably, the predicted targets by this approach were often involved in both beneficial and malicious signalling pathways, which may reflect heterogeneous cellular origins of EVs in tissues. Lastly, there has been an active debate on U6 whether it is a proper control. Through further analysis of EV miR profiles, miR‐676 was identified as a superior reference control due to its consistent and abundant expressions. In summary, our results contribute to identifying specific EV miRs for the potential therapeutic targets in heart failure and suggest that miR‐676 as a new reference control for the EV miR studies.
Highlights
Cardiomyocyte is a major contributor to cardiac composition and output
Our results demonstrated that the cardiac extracellular vesicles (EVs) contain diverse miRs with contradictory functions
As EVs are highlighted as an important mediator of cell-to-cell communications during heart failure, it becomes essential to analyse the contents of cardiac EVs
Summary
A heart is a highly complex structure composed of multiple types of cellular and acellular tissues. Of cardiac components, cardiomyocyte is a major contributor to cardiac composition and output. Non-myocytes such as fibroblasts, leucocytes and endothelial cells serve as a spatial buffer and more importantly modulate cardiomyocyte functions in response to physiological and pathological stimuli. EVs derived from stem cells or cardiac progenitor cells were generally beneficial, whereas EVs from fibroblasts or endothelial cells exhibited deleterious effects on cardiac functions.. EVs derived from stem cells or cardiac progenitor cells were generally beneficial, whereas EVs from fibroblasts or endothelial cells exhibited deleterious effects on cardiac functions.10–12 In these previous studies, the origin of EVs was confined to in vitro cultured cells or blood plasma, but the role of EVs in cardiac tissues has been poorly investigated. This study analysed miR profiles in the cardiac EVs isolated from murine normal and failing hearts. Our study may contribute to understand intercellular communication between cardiac cells under the pathological condition and suggests EV miRs as potential biomarkers and therapeutic targets for the intervention of heart failure
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