Objective "This project investigates the role of the beta3 adrenoceptor (β3-AR) in modulating the remodeling of the myocardium submitted to stress. Promising advances have been made in the host laboratory in showing that overexpression of the β3-AR in cardiac myocytes confers protection from pro-hypertrophic stimulus induced-remodeling. Preliminary data suggest that nitric oxide (NO) production by NO synthase (NOS), which is known to be coupled to the β3-AR signalling in the heart, is necessary for this protection to occur.Our central hypothesis therefore is that the activation of the β3-AR protects against hypertrophic remodeling of the heart through NOS and, possibly protein kinase G (PKG) -dependent mechanisms.The following stages of the research project will aim at 1) exploring the ability of the β3-AR to regulate remodeling in response to hemodynamic stresses of different severity; 2) ascertaining the specific role of the NOS isoform(s) in this protection; 3) unravelling the downstream effectors involved in the protective effects conferred by β3-AR activation; 4) investigating the co-localization of these key effectors with β3-AR in cellular microdomains, including caveolae; 5) studying the stage-specific- role of β3-AR signalling in the regulation of remodelling and function of stressed hearts from an inducible, cardiac specific, knockout mouse model.These experiments will enhance our understanding of the pathophysiologic role of beta3-adrenoceptors, which are upregulated in the remodeling heart, opening the way for new therapeutic modalities for cardiac remodeling using agonists at these receptors." Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2011-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator UNIVERSITE CATHOLIQUE DE LOUVAIN EU contribution € 169 800,00 Address PLACE DE L UNIVERSITE 1 1348 Louvain La Neuve Belgium See on map Region Région wallonne Prov. Brabant Wallon Arr. Nivelles Activity type Higher or Secondary Education Establishments Administrative Contact Jean-Luc Balligand (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
