Extracellular vesicles in cardiomyopathies: A narrative review

Abstract

Extracellular vesicles (EVs) are membrane-bound particles released by all cells under physiological and pathological conditions. EVs constitute a potential tool to unravel cell-specific pathophysiological mechanisms at the root of disease states and retain the potential to act as biomarkers for cardiac diseases. By being able to carry bioactive cargo (such as proteins and miRNAs), EVs harness great potential as accessible "liquid biopsies", given their ability to reflect the state of their cell of origin. Cardiomyopathies encompass a variety of myocardial disorders associated with mechanical, functional and/or electric dysfunction. These diseases exhibit different phenotypes, including inappropriate ventricular hypertrophy, dilatation, scarring, fibro-fatty replacement, dysfunction, and may stem from multiple aetiologies, most often genetic. Thus, the aims of this narrative review are to summarize the current knowledge on EVs and cardiomyopathies (e.g., hypertrophic, dilated and arrhythmogenic), to elucidate the potential role of EVs in the paracrine cell-to-cell communication among cardiac tissue compartments, in aiding the diagnosis of the diverse subtypes of cardiomyopathies in a minimally invasive manner, and finally to address whether certain molecular and phenotypical characteristics of EVs may correlate with cardiomyopathy disease phenotype and severity.

Keywords: Arrhythmogenic cardiomyopathy; Cardiomyopathies; Dilated cardiomyopathy; Extracellular vesicles; Hypertrophic cardiomyopathy.

Fig. 1

Circulating Extracellular vesicles. Extracellular vesicles (EVs) are phospholipid-bilayer membrane-enclosed nanoparticles released by all cell types into most biological fluids. They constitute a readily accessible snapshot of the physiological state of their originating donor cell, owing to their ability to carry cell-specific molecular cargo (e.g., nucleic acids and proteins). CD, cluster of differentiation.

Fig. 2

Echocardiographic representation of HCM, DCM and ARVC phenotypes. Panel A displays a parasternal long-axis echocardiographic view showing a patient affected by severe HCM with typical asymmetric hypertrophy involving the interventricular septum. Panel B displays an apical four-chamber echocardiographic view showing the heart of a patient with DCM, with an extremely dilated left ventricle (volume was 142 mL/m²). Panel C displays late gadolinium enhancement by CMR imaging of a patient affected by ARVC. A dilated right ventricle with extensive wall fibrosis (yellow arrow) and free-wall bulging (red arrows) can be appreciated. HCM, hypertrophic cardiomyopathy; DCM, dilated cardiomyopathy; ARVC, arrhythmogenic right ventricular cardiomyopathy; LV, left ventricle, LA, left atrium; RA, right atrium; RV, right ventricle.