Influence of ex vivo perfusion on the biomolecular profile of rat lungs

The FASEB JournalVolume 32, Issue 10 p. 5532-5549 ResearchFree to Read Influence of ex vivo perfusion on the biomolecular profile of rat lungs Caterina Lonati, Corresponding Author Caterina Lonati [email protected] Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Correspondence: Center for Surgical Research, Fondazione IRCCS Ca′ Granda-Ospedale Maggiore Policlinico, 9 Pace St., 20122 Milan, Italy. E-mail: [email protected]Search for more papers by this authorGiulia A. Bassani, Giulia A. Bassani Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, ItalySearch for more papers by this authorDaniela Brambilla, Daniela Brambilla Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, ItalySearch for more papers by this authorPatrizia Leonardi, Patrizia Leonardi Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this authorAndrea Carlin, Andrea Carlin Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this authorAlice Faversani, Alice Faversani Division of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this authorStefano Gatti, Stefano Gatti Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, ItalySearch for more papers by this authorFranco Valenza, Franco Valenza Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this author Caterina Lonati, Corresponding Author Caterina Lonati [email protected] Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Correspondence: Center for Surgical Research, Fondazione IRCCS Ca′ Granda-Ospedale Maggiore Policlinico, 9 Pace St., 20122 Milan, Italy. E-mail: [email protected]Search for more papers by this authorGiulia A. Bassani, Giulia A. Bassani Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, ItalySearch for more papers by this authorDaniela Brambilla, Daniela Brambilla Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, ItalySearch for more papers by this authorPatrizia Leonardi, Patrizia Leonardi Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this authorAndrea Carlin, Andrea Carlin Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this authorAlice Faversani, Alice Faversani Division of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this authorStefano Gatti, Stefano Gatti Center for Surgical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, ItalySearch for more papers by this authorFranco Valenza, Franco Valenza Center for Preclinical Investigation, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca′ Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Pathophysiology and Transplantation and Dental Sciences, University of Milan, Milan, ItalySearch for more papers by this author First published: 02 May 2018 https://doi.org/10.1096/fj.201701255RCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL ABSTRACT Despite increasing clinical adoption, biologic influences of ex vivo lung perfusion (EVLP) remain insufficiently elucidated. The aim of the current study was to investigate biomolecular changes induced by EVLP in rat lungs. EVLP was maintained for 180 min. Hyaluronan, mediators, and cells were assessed in the perfusate. Gene expression, signaling pathways, and ATP content were investigated in lung tissue. EVLP induced the release of medium-high molecular weight hyaluronan and transcription of hyaluronan synthases (P < 0.001). Increasing concentrations of inflammatory mediators were detected in the perfusate (P < 0.001). Perfused lungs exhibited a distinctive transcriptional signature compared with organs examined before or after surgery/procurement (P = 0.003). Up-regulated genes were involved in inflammation and its regulation, apoptosis/survival, heat shock, and oxidative stress response (q = 0). Down-regulated genes were related to lymphocyte function (q = 0). The NF-κB, signal transducer and activator of transcription 3, ERK1/2, p38, Akt, and stress- activated protein kinase/JNK signaling pathways were modulated by EVLP (P < 0.05). Most of these biomolecular changes were examined and confirmed in additional experiments that were performed in lungs procured from donation after cardiocirculatory death after 180 min of warm ischemia. The current study demonstrates that EVLP broadly affects the lung biomolecular phenotype. These findings improve our comprehension of the effects exerted by the procedure and encourage additional research in preclinical models to implement therapeutic interventions.—Lonati, C., Bassani, G. A., Brambilla, D., Leonardi, P., Carlin, A., Faversani, A., Gatti, S., Valenza, F. Influence of ex vivo perfusion on the biomolecular profile of rat lungs. FASEB J. 32, 5532–5549 (2018). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2fj201701255r-sup-0001.docxapplication/docx, 23.5 KB Supplementary Material fsb2fj201701255r-sup-0002.docxapplication/docx, 19.4 KB Supplementary Material fsb2fj201701255r-sup-0003.pdfPDF document, 112.2 KB Supplementary Material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume32, Issue10October 2018Pages 5532-5549 RelatedInformation