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.

Keywords: biomarkers; cardiovascular diseases; exosomes; extracellular vesicles; mass spectrometry; proteins.

Figure 1

Different route of the release of extracellular vesicles (EVs). Schematic representation of the origin and release of EVs. Exosomes originate from the endosomal compartment as intraluminal vesicles (ILVs) in multivesicular bodies (MVBs), then released into the extracellular environment upon their fusion with the plasma membrane. Microvesicles (MVs) arise from the outward budding of the plasma membrane mediated by cytoskeletal remodelling and phospholipid rearrangements. Apoptotic bodies, instead, bleb consequently to cell death as a result of increased hydrostatic pressure after cell contraction.

Figure 2

Potential applications of extracellular vesicles (EVs). Involvement of EVs in the pathogenesis and progression of several diseases. Based on these effects, EVs can be translated into therapeutic targets and useful disease biomarkers. Further, their role in the maintenance of fundamental physiological processes like blood coagulation, stem cell plasticity, and tissue repair supports their potential application as therapeutic agents. Finally, EVs can transfer their contents to target cells, thus providing their possible use as a drug delivery system.

Figure 3

Venn diagram for exosome proteins identified in human studies. (a) Overlapping of proteins identified from different cell-derived exosomes. VSMC, vascular smooth muscle cells (blue); EC, endothelial cells (yellow); MSC, mesenchymal stem cells (green); CPC, cardiac derived progenitor stem cells (red). (b) Overlapping between identified proteins in exosome derived from cell cultures (blue) or from biological fluids (yellow).