Plasma-derived extracellular vesicles released after endurance exercise exert cardioprotective activity through the activation of antioxidant pathways
Veronica Lisi,
Giorgia Senesi,
Nadia Bertola,
Matteo Pecoraro,
Sara Bolis,
Alice Gualerzi,
Silvia Picciolini,
Andrea Raimondi,
Cristina Fantini,
Elisa Moretti,
Attilio Parisi,
Paolo Sgrò,
Luigi Di Luigi,
Roger Geiger,
Silvia Ravera,
Giuseppe Vassalli,
Daniela Caporossi,
Carolina Balbi
Affiliations
Veronica Lisi
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy
Giorgia Senesi
Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
Nadia Bertola
Department of Experimental Medicine, University of Genoa, 16132, Genova, Italy
Matteo Pecoraro
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
Sara Bolis
Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Alice Gualerzi
Laboratory of Nanomedicine and Clinical Biophotonics (LABION), IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
Silvia Picciolini
Laboratory of Nanomedicine and Clinical Biophotonics (LABION), IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
Andrea Raimondi
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland; Centro Imaging Sperimentale, IRCCS Istituto Scientifico San Raffaele, Via Olgettina 52, 20132, Milan, Italy
Cristina Fantini
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy
Elisa Moretti
Laboratory of Physical Exercise and Sport Science, Department of Exercise, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy
Attilio Parisi
Laboratory of Physical Exercise and Sport Science, Department of Exercise, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy
Paolo Sgrò
Laboratory of Physical Exercise and Sport Science, Department of Exercise, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy
Luigi Di Luigi
Endocrinology Unit, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy
Roger Geiger
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
Silvia Ravera
Department of Experimental Medicine, University of Genoa, 16132, Genova, Italy
Giuseppe Vassalli
Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Center for Molecular Cardiology, Zurich, Switzerland
Daniela Caporossi
Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy
Carolina Balbi
Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Center for Molecular Cardiology, Zurich, Switzerland; Corresponding author. Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
Cardiovascular diseases (CVD) can cause various conditions, including an increase in reactive oxygen species (ROS) levels that can decrease nitric oxide (NO) availability and promote vasoconstriction, leading to arterial hypertension. Physical exercise (PE) has been found to be protective against CVD by helping to maintain redox homeostasis through a decrease in ROS levels, achieved by increased expression of antioxidant enzymes (AOEs) and modulation of heat shock proteins (HSPs). Extracellular vesicles (EVs) circulating in the body are a major source of regulatory signals, including proteins and nucleic acids. Interestingly, the cardioprotective role of EVs released after PE has not been fully described.The aim of this study was to investigate the role of circulating EVs, obtained through Size Exclusion Chromatography (SEC) of plasma samples from healthy young males (age: 26.95 ± 3.07; estimated maximum oxygen consumption rate (VO2max): 51.22 ± 4.85 (mL/kg/min)) at basal level (Pre_EVs) and immediately after a single bout of endurance exercise (30’ treadmill, 70% heart rate (HR) -Post_EVs). Gene ontology (GO) analysis of proteomic data from isolated EVs, revealed enrichment in proteins endowed with catalytic activity in Post_EVs, compare to Pre_EVs, with MAP2K1 being the most significantly upregulated protein. Enzymatic assays on EVs derived from Pre and Post samples showed increment in Glutathione Reductase (GR) and Catalase (CAT) activity in Post_EVs. At functional level, Post_EVs, but not Pre_EVs, enhanced the activity of antioxidant enzymes (AOEs) and reduced oxidative damage accumulation in treated human iPS-derived cardiomyocytes (hCM) at basal level and under stress conditions (Hydrogen Peroxide (H2O2) treatment), resulting in a global cardioprotective effect.In conclusion, our data demonstrated, for the first time, that a single 30-min endurance exercise is able to alter the cargo of circulating EVs, resulting in cardioprotective effect through antioxidant activity.
