Proteomics of Extracellular Vesicles: Update on Their Composition, Biological Roles and Potential Use as Diagnostic Tools in Atherosclerotic Cardiovascular Diseases

Abstract

Extracellular vesicles (EVs) are lipid-bound vesicles released from cells under physiological and pathological conditions. Basing on biogenesis, dimension, content and route of secretion, they can be classified into exosomes, microvesicles (MVs) and apoptotic bodies. EVs have a key role as bioactive mediators in intercellular communication, but they are also involved in other physiological processes like immune response, blood coagulation, and tissue repair. The interest in studying EVs has increased over the years due to their involvement in several diseases, such as cardiovascular diseases (CVDs), and their potential role as biomarkers in diagnosis, therapy, and in drug delivery system development. Nowadays, the improvement of mass spectrometry (MS)-based techniques allows the characterization of the EV protein composition to deeply understand their role in several diseases. In this review, a critical overview is provided on the EV’s origin and physical properties, as well as their emerging functional role in both physiological and disease conditions, focusing attention on the role of exosomes in CVDs. The most important cardiac exosome proteomic studies will be discussed giving a qualitative and quantitative characterization of the exosomal proteins that could be used in future as new potential diagnostic markers or targets for specific therapies.

A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine

“…As pronounced, the EVs can be generated by a spectrum of various cell types and they can be obtained from biological fluids and also conditioned medium (CM) [64,65]. A distinctive procedure of MS-based proteomic examinations of EVs includes multiple stages, such as the separation of EVs from particular biofluids, the extraction of EV proteins utilizing lysis buffers, and the separation of the extracted proteins and digestion before the MS analysis [66]. Especially, the isolated EV proteins can be separated using gel electrophoresis and in-gel digestion.…”

“…Especially, the isolated EV proteins can be separated using gel electrophoresis and in-gel digestion. Further, they can be directly digested and then achieved peptides are fractionated by liquid chromatography (LC) before the MS analysis [ 66 ].…”

Circulating Extracellular Vesicles As Biomarkers and Drug Delivery Vehicles in Cardiovascular Diseases

“…The protein profile might change already in a very early stage of the disease, which makes this content a potential early biomarker [ 115 ]. The EV protein cargo is heterogenous and dependent on the cell type or biofluid of origin [ 138 ].…”

Extracellular vesicles in atherothrombosis and cardiovascular disease: Friends and foes

“…Finally, exosome therapy might be a potential candidate for regenerative cardiovascular medicine in the future [119], although the research is still at the preclinical stage. It has the advantage, compared to stem cells, that exosomes are more stable in the circulation and exert reduced (or negligible) immunogenic or tumorigenic effects [120]. However, a combination of two, or even more methods for EV isolation and extraction (i.e., size exclusion chromatography plus ultracentrifugation), may be employed to meet the standard requirements for the clinical use of EV extracts in humans, keeping also in mind that the extraction yield may be severely affected by the process.…”