{"id":"https://openalex.org/G4604452","display_name":"Activation of signaling pathways by oxidant stress in the anoxic-reoxygenated developing heart","description":"Congenital heart defects represent a major cause of morbidity andmortality in the first year of life. Although recent developments in fetalmedicine and basic research have significantly improved our understandingof fetal diseases, the precise pathological processes remain to beelucidated. The main goal of this project is to decipher the molecularmechanisms underlying the dysfunction of the developing heart when it issubjected to in utero deprivation (hypoxia) and readmission of oxygen(reoxygenation). The response of the immature myocardium tohypoxia-reoxygenation can indeed differ markedly from that of the adultheart. Furthermore, an adverse intrauterine environment, such as transientreduced oxygen delivery due to uteroplacental abnormalities, may be at theorigin of life-long cardiopathies, the so-called ' memory of the fetalheart '.<br><br>The proposed model is the spontaneously beating heartisolated from a 4-day-old chick embryo and subjected to in vitro hypoxiafollowed by reoxygenation. The myocardial dysfunction induced by anepisode of hypoxia-reoxygenation is partly due to an overproduction ofreactive oxygen species which are recognized as potentially deleteriousfree radicals but also as important intracellular mediators. The freeradicals are known to induce an oxidant stress and activate variouscellular signaling pathways. In particular, a series of essential enzymesnamed kinases are involved in cell survival or cell death.<br><br>Usingour experimental setup and molecular biology techniques, we will be ableto 1) characterize the electrical and contractile disturbances in theatrium and ventricle, 2) determine the time course of free radicalsproduction and, 3) know whether the myocardial injury is associated with acharacteristic pattern of kinase activation. Thus, the myocardialdysfunction will be correlated, in space and time, with oxidant stress andactivation of signaling pathways.<br><br>The expected results of thisproject could help to elaborate specific protective strategies for thediseased developing heart, especially in the context of recent advances infetal/neonatal cardiology and surgery.<br>","funder_award_id":"105901","funder":{"id":"https://openalex.org/F4320320924","display_name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi":"10.13039/501100001711"},"funded_outputs":["https://openalex.org/W176373426","https://openalex.org/W2017467571","https://openalex.org/W2086431820","https://openalex.org/W2165374059","https://openalex.org/W2500129446","https://openalex.org/W7057464273"],"funded_outputs_count":6,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":227000.0,"currency":"CHF","amount_usd":181849.05,"amount_usd_basis":"daily_rate","recipients":[{"id":"https://openalex.org/I97565354","display_name":"University of Lausanne","ror":"https://ror.org/019whta54","country_code":"CH","roles":["lead"],"share":null,"basis":"affiliation_matcher","asserted_by":"funder"}],"recipient_countries":[{"country_code":"CH","share":1.0,"amount_usd":181849.05,"basis":"organisation_location"}],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"Project funding","start_date":"2004-10-01","end_date":"2008-03-31","start_year":2004,"end_year":2008,"landing_page_url":"https://data.snf.ch/grants/grant/105901","doi":null,"provenance":"snsf","lead_investigator":{"given_name":"Raddatz,","family_name":"Eric","orcid":null,"role_start":null,"affiliation":{"name":"University of Lausanne \u2013 LA","country":"Switzerland","ids":null}},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G4604452","primary_topic":null,"topics":null,"institution_awarded":[{"id":"https://openalex.org/I97565354","display_name":"University of Lausanne","ror":"https://ror.org/019whta54","country_code":"CH","type":"education","lineage":["https://openalex.org/I97565354"]}],"updated_date":"2026-11-05T03:01:09.000Z","created_date":"2026-07-13T04:27:35.000Z"}