Methods for the identification and characterization of extracellular vesicles in cardiovascular studies: from exosomes to microvesicles

Author:

Davidson Sean M1ORCID,Boulanger Chantal M2ORCID,Aikawa Elena3ORCID,Badimon Lina4ORCID,Barile Lucio5ORCID,Binder Christoph J6ORCID,Brisson Alain7ORCID,Buzas Edit8ORCID,Emanueli Costanza9ORCID,Jansen Felix10ORCID,Katsur Miroslava1ORCID,Lacroix Romaric1112ORCID,Lim Sai Kiang1314ORCID,Mackman Nigel15ORCID,Mayr Manuel16ORCID,Menasché Philippe1718ORCID,Nieuwland Rienk1920ORCID,Sahoo Susmita21ORCID,Takov Kaloyan16ORCID,Thum Thomas2223ORCID,Vader Pieter224ORCID,Wauben Marca H M25ORCID,Witwer Kenneth2627ORCID,Sluijter Joost P G18ORCID

Affiliation:

1. The Hatter Cardiovascular Institute, University College London , WC1E 6HX London , UK

2. Université Paris Cité, Paris-Cardiovascular Research Center, INSERM , Paris , France

3. Department of Medicine, Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA 02115 , USA

4. Cardiovascular Science Program-ICCC, IR-Hospital de la Santa Creu i Santa Pau-IIBSantPau, CiberCV, Autonomous University of Barcelona , Barcelona , Spain

5. Laboratory for Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale and Faculty of Biomedical Sciences, Università Svizzera italiana , 6900 Lugano , Switzerland

6. Department of Laboratory Medicine, Medical University of Vienna , Vienna , Austria

7. Molecular Imaging and NanoBioTechnology, UMR-5248-CBMN, CNRS-University of Bordeaux-IPB , Bat. B14, Allée Geoffroy Saint-Hilaire, 33600 Pessac , France

8. Department of Genetics, Cell- and Immunobiology, Semmelweis University, HCEMM-SU and ELKH-SE Immune Proteogenomics Extracellular Vesicle Research Group , Budapest , Hungary

9. National Heart and Lung Institute, Imperial College London, Hammersmith Campus , London W12 0NN , UK

10. Department of Internal Medicine II, Heart Center, University Hospital Bonn , Bonn , Germany

11. Aix Marseille University, INSERM 1263, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en CardioVasculaire et Nutrition (C2VN) , Marseille , France

12. Department of Haematology and Vascular Biology, CHU La Conception, APHM , Marseille , France

13. Institute of Medical Biology and Institute of Molecular and Cell Biology, Agency for Science, Technology and Research , Singapore , Singapore

14. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore

15. Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill , Chapel Hill, NC , USA

16. King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences , London , UK

17. Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou , Paris , France

18. Laboratory of Experimental Cardiology, Department of Cardiology, UMC Utrecht Regenerative Medicine Center and Circulatory Health Laboratory, Utrecht University, University Medical Center Utrecht , Utrecht , The Netherlands

19. Vesicle Observation Center, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands

20. Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands

21. Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai , New York, NY , USA

22. Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School , Hannover , Germany

23. Fraunhofer Institute of Toxicology and Experimental Medicine , Hannover , Germany

24. CDL Research, University Medical Center Utrecht , Heidelberglaan 100, 3584 CX Utrecht , The Netherlands

25. Faculty of Veterinary Medicine, Department of Biomolecular Health Sciences, Utrecht University , Yalelaan 2, Utrecht , The Netherlands

26. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine , Baltimore, MD , USA

27. Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, MD , USA

Abstract

Abstract Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are released from cells of the cardiovascular system, and are considered important mediators of intercellular and extracellular communications. Two types of EVs of particular interest are exosomes and microvesicles, which have been identified in all tissue and body fluids and carry a variety of molecules including RNAs, proteins, and lipids. EVs have potential for use in the diagnosis and prognosis of cardiovascular diseases and as new therapeutic agents, particularly in the setting of myocardial infarction and heart failure. Despite their promise, technical challenges related to their small size make it challenging to accurately identify and characterize them, and to study EV-mediated processes. Here, we aim to provide the reader with an overview of the techniques and technologies available for the separation and characterization of EVs from different sources. Methods for determining the protein, RNA, and lipid content of EVs are discussed. The aim of this document is to provide guidance on critical methodological issues and highlight key points for consideration for the investigation of EVs in cardiovascular studies.

Funder

Hatter Foundation

British Heart Foundation

European Research Council

Dutch Ministry of Economic Affairs

Netherlands CardioVascular Research Initiative

Dutch Heart Foundation

French National Agency for Research

Fondation pour la Recherche M

dicale

Austrian Science Fund

EU Horizon 2020

Spanish Ministry of Economy and Competitiveness of Science

Carlos III Institute of Health

FEDER

Fundación Investigación Cardiovascular-Fundación Jesus Serra

Deutsche Forschungsgemeinschaft

German Research Foundation

Corona Foundation

National Institutes of Health

US NIH National Cancer Institute

Office of the Director

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

Reference189 articles.

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3. Exosomes: the future of biomarkers in medicine;Properzi;Biomark Med,2013

4. The role of microvesicles and its active molecules in regulating cellular biology;Lv;J Cell Mol Med,2019

5. 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;Sluijter;Cardiovasc Res,2018

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