# Effect of Physical Exercise on the Release of Micorparticles with Angiogenic Potential
## 3 Extracellular Vesicles Classification  
Human cells are able to release various types of membrane vesicles in response to different stimuli, generally called extracellular vesicles (EVs). EVs include exosomes, MPs (also called microcresicles), and apoptotic bodies [28] (Table 1).  
Exosomes are vesicles surrounded by a double layer of phospholipids and their size ranges between 50 and 100 nm in diameter. They are released in both physiological condition and upon activation by exocytosis of multivesicular bodies (MVBs) [29]. Exosomes can communicate with other cells either through a direct contact between surface proteins or by vesicles-cell membrane fusion or by endocytosis. They expose phosphatidylserine (PS) on the external membrane and various markers such as LAMP1, TSG101, CD63, CD81, and CD9 [30]. The main functions of exosomes include antigen presentation and immunostimulatory activity. In addition, exosomes are able to horizontally transfer mRNA and miRNA as well as oncogenic receptors [31].  
MPs, formerly described as \"platelet dust\", are now well known cell-cell communicators and they act as signaling molecules in physiological homeostatic processes or as a consequence of pathological condition including diabetes, chronic kidney disease, rheumatoid arthritis, multiple sclerosis, and cardiovascular diseases [32]. MPs are found in most body fluids such as plasma, saliva, urine, and cerebrospinal fluid. They represent a heterogeneous population of vesicular-like structures composed by a phospholipid bilayer and their sizes range from 100 nm to 1 \(\upmu\)m in diameter; however precise cut-off values remain to be established. MPs found in bloodstream may originate from various vascular cells (e.g., platelets, monocytes, erythrocytes, granulocytes) [33]. However, among all circulating MPs, platelet-derived MPs (Plt-MPs) are the most abundant population, representing 70-90% of the total [34]. They are produced by budding of the plasma membrane, in a process called endocytosis. After their release, MPs carry proteins that are signature of their cell of origin, and transport various enzymes, RNA, and miRNA [35]. MPs generally expose PS on their outer leaflet (Annexin V\({}^{+}\)), however some evidence shows that MPs can also be PS negative [36]. In addition, a subpopulation of various phenotypes of MPs expose tissue factor [37]. The release of MPs is induced upon cell activation or apoptosis.  
Apoptotic bodies are EVs larger than MPs and exosomes. Their sizes range from 500 nm to 3 \(\upmu\)m and they expose PS; however, their outer membrane differs from MPs due to its permeability [38]. Apoptotic bodies are released by membrane blebbing of cells undergoing apoptosis and they may horizontally transfer their content, such as cell organelles, fragmented DNA, and oncogenes.  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**EVs Types** & **Size** & **Surface Markers** &
\begin{tabular}{c} **Mechanism of** \\ **Production** \\ \end{tabular} & **Content** \\ \hline \multirow{8}{*}{Exosomes} & & Phosphatidylserine & & \\  & & (PS, Annexin V\({}^{+}\)), & & \\  & & Lysosomal-Associated & & \\  & & Membrane Protein 1 & & \\  & & (LAMP1), Tumor & & Fusion of late & \\  & & Susceptibility 101 & endosomes/multivisicular & Proteins, RNAs, \\  & & (TSG101), & bodies (MVBs) with the & miRNAs \\  & & Granulopynis (CD63), & plasma membrane & \\  & & Target of & & \\  & & antiproliferative & & \\  & & antibody 1 (CD81), & & \\  & & Tetraspanin-29 (CD9) & & \\ Microparticles & 100 nm–1 \(\upmu\)m & PS \({}^{*}\) (Annexin V\({}^{+}\)) & Budding/blebbing of the & Proteins, RNAs, \\  & & markers of parental cell & plasma membrane & miRNAs \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\  & & & & \\ \hline \hline \end{tabular}
\end{table}
Table 1: General characteristics of extracellular vesicles (EVs).