In the cell culture experimental part of our project, we have completed much of the cell culture work including protein and RNA analyses, respectively, in lung alveolar cells and pulmonary vascular endothelial cells. Our data so far show significant regulation of the DDAH/ADMA/NO pathway in lung alveolar cells during hypoxia, which is a novel finding. Much less regulation occurs in pulmonary endothelial cells. We have also completed the Next Generation RNA Sequencing experiments as planned in order to address the signaling pathways and redox mechanisms involved. Currently, bioinformatics-based data analysis of this data set is ongoing. The next step will be the experimental validation of our findings. We have successfully generated two new lines of cell type-specifically genetically modified mice; these animals are currently being subjected to experimental hypoxia in order to study the changes in the lungs, heart, and blood vessels. A first clinical study with humans has also already been completed; after genetic screening of more than 200 healthy young men and women, we have successfully recruited four genetically characterized groups of healthy men and women to participate in the clinical study at the High Altitude Research Station Jungfraujoch at 3,450 M above sea level. Each participant completed a baseline study at sea level as well as repeat studies on days 1 to 7 of high altitude exposure according to our study protocol. Data analyses and biochemical analyses of the acquired frozen samples are currently ongoing. Finally, we have advanced quite far regarding the final work package that focuses on translation of our experimental findings to COPD patients. For one, we have completed biomarker analysis in a large, multinational European Survey on lung health, from which we received biosamples and access to follow-up data. In this study, data analysis is ongoing. Second, we have signed an agreement with the steering committee of the world’s largest study on COPD, from which we will receive several thousand blood samples for analysis and conduct data analysis to validate our hypothesis on the association of intermittent hypoxaemia, biomarkers, and disease progression in this large cohort of COPD patients. The next step here, after receipt of the sample shipment, will be biomarker measurements that will keep our laboratory busy during the forthcoming year, followed by statistical analyses.
