Obiettivo Cardiac muscle death, without equivalent cardiomyocyte replacement, results in severe deficiencies in cardiac pump function both after myocardial infarction and in those chronic cardiomyopathies where apoptosis is prevalent. For this reason, understanding the molecular events that allow but severely limit cardiac regeneration in heart disease is of fundamental importance and may also hold immense translational potential.The ATP-Binding Cassette Transporter Abcg2 is expressed in various healthy organs and protects, against toxic compounds and their metabolites as well as against hypoxia and oxidative stress, conditions present during ischemic heart injury. Abcg2 is a common marker of tissue progenitor cells, including the dormant stem cells in adult mouse and human heart. Abcg2 plays a pivotal role in cardiac repair following infarction in mice, which to date has been ascribed to its protection of endothelial cells, the other site of Abcg2 expression in the heart. Its function in cardiac progenitor cells remains to be tested conclusively.With the use of genetically modified mice and fate-mapping techniques, this study will determine the functional role of an ATP-binding cassette transporter, Abcg2, in the clonogenicity of heart-derived progenitor cells in culture and the contribution of cells expressing this protein in new myocyte creation after myocardial infarction. We will: (1) Determine the role of Abcg2 in cardiac progenitor cells’ function, as defined by in vitro studies of clonal growth and its relationship with hyperoxic stress in culture, by disruption of Abcg2 in adult mice or isolated cells. (2) Establish whether conditional disruption of Abcg2 in adult mice influences cardiac function during recovery from experimental myocardial infarction. (3) Define the contribution of Abcg2-positive cells to cardiac myocyte creation after myocardial infarction, using fate mapping techniques with tamoxifen-dependent Cre recombinase driven by the Abcg2 locus. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cells Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Invito a presentare proposte FP7-PEOPLE-2012-IEF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IEF - Intra-European Fellowships (IEF) Coordinatore IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Contributo UE € 299 558,40 Indirizzo SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Regno Unito Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Tatjana Palalic (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
