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Review
. 2018 Jan 1;114(1):19-34.
doi: 10.1093/cvr/cvx211.

Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology

Joost Petrus Gerardus Sluijter  1 , Sean Michael Davidson  2 , Chantal M Boulanger  3 , Edit Iren Buzás  4   5 , Dominique Paschalis Victor de Kleijn  6   7 , Felix Benedikt Engel  8 , Zoltán Giricz  9 , Derek J Hausenloy  10   11   12   13   14   15 , Raj Kishore  16 , Sandrine Lecour  17 , Jonathan Leor  18 , Rosalinda Madonna  19   20   21 , Cinzia Perrino  22 , Fabrice Prunier  23 , Susmita Sahoo  24 , Ray Michel Schiffelers  25 , Rainer Schulz  26 , Linda Wilhelmina Van Laake  27 , Kirsti Ytrehus  28 , Péter Ferdinandy  29   30
Affiliations
Review

Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology

Joost Petrus Gerardus Sluijter et al. Cardiovasc Res. .

Abstract

Extracellular vesicles (EVs)-particularly exosomes and microvesicles (MVs)-are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized. These capabilities include transporting regulatory molecules including different RNA species, lipids, and proteins through the extracellular space including blood and delivering these cargos to recipient cells to modify cellular activity. EVs powerfully stimulate angiogenesis, and can protect the heart against myocardial infarction. They also appear to mediate some of the paracrine effects of cells, and have therefore been proposed as a potential alternative to cell-based regenerative therapies. Moreover, EVs of different sources may be useful biomarkers of cardiovascular disease identities. However, the methods used for the detection and isolation of EVs have several limitations and vary widely between studies, leading to uncertainties regarding the exact population of EVs studied and how to interpret the data. The number of publications in the exosome and MV field has been increasing exponentially in recent years and, therefore, in this ESC Working Group Position Paper, the overall objective is to provide a set of recommendations for the analysis and translational application of EVs focussing on the diagnosis and therapy of the ischaemic heart. This should help to ensure that the data from emerging studies are robust and repeatable, and optimize the pathway towards the diagnostic and therapeutic use of EVs in clinical studies for patient benefit.

Keywords: Cardioprotection; Co-morbidities; Exosomes; Extracellular vesicles; Heart failure; Ischaemia; Microvesicles; Postconditioning; Preconditioning; Regenerative medicine; Remote conditioning; Reperfusion.

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Figures

Figure 1
Figure 1
Exosomes and MVs overlap in size with VLDL and chylomicrons, and in density with HDL/LDL particles. Exosome density is typically 1.06–1.20 g/mL. MV density is not well defined but they have been found between ∼1.03–1.08 g/mL.
Figure 2
Figure 2
The major classes of EV. Typical size and density of EV classes and some of the contaminants that may be co-isolated, depending on biofluid.
Figure 3
Figure 3
Standard techniques used for isolating exosomes from other EVs, protein, and lipoproteins present in blood and cell-culture medium.
Figure 4
Figure 4
Standard methods of characterizing EVs. (A) Transmission electron microscopy (TEM) of negative-stained EVs reveals the ‘cup-shaped’ appearance of exosomes (E) and MVs once they have been dried for TEM (they are spherical in solution). (B) The spherical appearance of lipoprotein particles by TEM is quite distinct (image courtesy of Robert L. Hamilton and the Arteriosclerosis Specialized Center of Research, University of California, San Francisco). (C) Nanoparticle tracking analysis (NTA) provides a size distribution of particles based on calculating their size by their random Brownian motion. (D, E) Tuneable resistance pulse sensing (TRP) determines size distribution by the change in resistance as the particle crosses a small pore in a membrane (which is selected according to the size range examined).
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