Extracellular Vesicle-Derived Non-Coding RNAs: Key Mediators in Remodelling Heart Failure

Abstract

Heart failure (HF), a syndrome of persistent development of cardiac insufficiency due to various heart diseases, is a serious and lethal disease for which specific curative therapies are lacking and poses a severe burden on all aspects of global public health. Extracellular vesicles (EVs) are essential mediators of intercellular and interorgan communication, and are enclosed nanoscale vesicles carrying biomolecules such as RNA, DNA, and proteins. Recent studies have showed, among other things, that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long ncRNAs (lncRNA), and circular RNAs (circRNAs) can be selectively sorted into EVs and modulate the pathophysiological processes of HF in recipient cells, acting on both healthy and diseased hearts, which makes them promising targets for the diagnosis and therapy of HF. This review aims to explore the mechanism of action of EV-ncRNAs in heart failure, with emphasis on the potential use of differentially expressed miRNAs and circRNAs as biomarkers of cardiovascular disease, and recent research advances in the diagnosis and treatment of heart failure. Finally, we focus on summarising the latest advances and challenges in engineering EVs for HF, providing novel concepts for the diagnosis and treatment of heart failure.

Keywords: biogenesis; engineered extracellular vesicles; exosome; extracellular vesicles; heart failure; microRNA; non-coding RNA.

Figure 1

The main structure and classification of extracellular vesicles (EVs), the contents it carries such as ncRNAs. Mechanisms of EVs biogenesis and uptake.

Figure 2

ncRNA classifications. RNAs are classified into two broad categories: messenger RNA (mRNA) and non-coding RNA (ncRNA).

Figure 3

Clinical applications of drug-loaded exosomes and biogenesis and mechanism of action of exosomes. Engineered exosomes can deliver drugs or nucleic acids to target cells or tissues, modulating their biological functions and achieving therapeutic effects.