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

Sean M Davidson; Chantal M Boulanger; Elena Aikawa; Lina Badimon; Lucio Barile; Christoph J Binder; Alain Brisson; Edit Buzas; Costanza Emanueli; Felix Jansen; Miroslava Katsur; Romaric Lacroix; Sai Kiang Lim; Nigel Mackman; Manuel Mayr; Philippe Menasché; Rienk Nieuwland; Susmita Sahoo; Kaloyan Takov; Thomas Thum; Pieter Vader; Marca H M Wauben; Kenneth Witwer; Joost P G Sluijter

doi:10.1093/cvr/cvac031

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

Cardiovasc Res. 2023 Mar 17;119(1):45-63. doi: 10.1093/cvr/cvac031.

Authors

Sean M Davidson¹, Chantal M Boulanger², Elena Aikawa³, Lina Badimon⁴, Lucio Barile⁵, Christoph J Binder⁶, Alain Brisson⁷, Edit Buzas⁸, Costanza Emanueli⁹, Felix Jansen¹⁰, Miroslava Katsur¹, Romaric Lacroix^{11

12}, Sai Kiang Lim^{13

14}, Nigel Mackman¹⁵, Manuel Mayr¹⁶, Philippe Menasché^{17

18}, Rienk Nieuwland^{19

20}, Susmita Sahoo²¹, Kaloyan Takov¹⁶, Thomas Thum^{22

23}, Pieter Vader^{2

24}, Marca H M Wauben²⁵, Kenneth Witwer^{26

27}, Joost P G Sluijter¹⁸

Affiliations

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

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.

Keywords: Biodistribution; Blood; Cardiovascular diseases; Exosomes; Extracellular vesicle composition; Heart; Microvesicles; Therapeutics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cardiovascular System*
Cell-Derived Microparticles* / metabolism
Exosomes* / metabolism
Extracellular Vesicles* / metabolism
Humans
Myocardial Infarction* / metabolism
RNA / metabolism

Substances

RNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding