Objective NO PRESSURE will address the hypothesis that intermittent hypoxaemia is a major driver of the pulmonary pathophysiology and the systemic co-morbidity that is present at a sub-clinical level already in early disease stages of a significant sub-group of COPD patients with a high risk of rapidly declining lung function and poor prognosis. The project has been conceptualized to achieve ground-breaking scientific insight into the role of intermittent hypoxaemia as a driver of COPD progression and outcome via dysfunction of the L-arginine-ADMA-NO pathway. Its five work packages will span from molecular regulation of the pulmonary L-arginine-ADMA-NO pathway in hypoxia to cellular oxygen sensing and signal transduction mechanisms, via translational studies in genetically modified mouse models and genotyped healthy humans, to clinical proof-of-concept studies of exercise-induced, intermittent hypoxaemia as a diagnostic indicator to identify a subgroup of high-risk COPD patients and the ability to therapeutically intervene by pharmacological modification of the L arginine-ADMA-NO pathway.Combining state-of-the-art molecular biology techniques, specifically designed genetically engineered animal models, and translation of the obtained results into genomically characterized humans who will be exposed to hypoxia, NO PRESSURE will achieve a unique level of depth in our understanding of the molecular pathophysiology of the lung’s response to hypoxia with proven relevance to human biology. Beyond this, NO PRESSURE will take the step towards validation of pathophysiologically proven biomarkers and, thus, molecular mechanisms in the world’s unique long-term prospective cohort for lung disease. In addition, it will deliver unequivocal evidence for clinical utility in two small, but well defined COPD patient cohorts, with one having a focus on prognostic relevance and the other one opening the avenue towards future pharmacotherapeutic intervention to improve prognosis. Fields of science medical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesmolecular biology Keywords hypoxic gene expression nitric oxide ADMA asymmetric dimethylarginine oxygen sensing exertional hypoxaemia biomarker Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2022-ADG - ERC ADVANCED GRANTS Call for proposal ERC-2022-ADG See other projects for this call Funding Scheme HORIZON-ERC - HORIZON ERC Grants Host institution UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Net EU contribution € 2 499 927,00 Address Martinistrasse 52 20251 Hamburg Germany See on map Region Hamburg Hamburg Hamburg Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 499 927,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Germany Net EU contribution € 2 499 927,00 Address Martinistrasse 52 20251 Hamburg See on map Region Hamburg Hamburg Hamburg Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 499 927,00
