Extracellular vesicles: biomarkers and regulators of vascular function during extracorporeal circulation

// Mark J. McVey 1, 2, 3, 4 and Wolfgang M. Kuebler 1, 2, 5, 6, 7 1 Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, ON, Canada 2 Department of Physiology, University of Toronto, Toronto, ON, Canada 3 Department of Anesthesia, University of Toronto, Toronto, ON, Canada 4 Department of Anesthesia and Pain Medicine, SickKids, Toronto, ON, Canada 5 Department of Surgery, University of Toronto, Toronto, ON, Canada 6 Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany 7 German Heart Institute, Berlin, Germany Correspondence to: Wolfgang M. Kuebler, email: wolfgang.kuebler@charite.de Keywords: extracellular vesicles; extracorporeal circuits; ECMO; cardiopulmonary bypass; hemodialysis Received: May 26, 2018      Accepted: November 26, 2018      Published: December 14, 2018 ABSTRACT Extracellular vesicles (EVs) are generated at increased rates from parenchymal and circulating blood cells during exposure of the circulation to abnormal flow conditions and foreign materials associated with extracorporeal circuits (ExCors). This review describes types of EVs produced in different ExCors and extracorporeal life support (ECLS) systems including cardiopulmonary bypass circuits, extracorporeal membrane oxygenation (ECMO), extracorporeal carbon dioxide removal (ECCO 2 R), apheresis, dialysis and ventricular assist devices. Roles of EVs not only as biomarkers of adverse events during ExCor/ECLS use, but also as mediators of vascular dysfunction are explored. Manipulation of the number or subtypes of circulating EVs may prove a means of improving vascular function for individuals requiring ExCor/ECLS support. Strategies for therapeutic manipulation of EVs during ExCor/ECLS use are discussed such as accelerating their clearance, preventing their genesis or pharmacologic options to reduce or select which and how many EVs circulate. Strategies to reduce or select for specific types of EVs may prove beneficial in preventing or treating other EV-related diseases such as cancer.