Conclusion
This study provided insight into the changes in molecular events during the transition from acute to extended low pO2 exposure in the lung and plasma proteome. The molecular events which respond to extended low pO2 exposure are Cytoskeletal re-modeling, energy metabolism, redox homeostasis and innate immunity/inflammation (Fig. 7). STAT3 was observed to play a connecting role between the molecular occurrences in the lung and the systemic proteomic response during extended low pO2 exposure. We identified three pathways that can provide biomarkers and therapeutic targets against extended low pO2 exposures at altitude. These are cytoskeletal elements, energy metabolism and inflammation. Normalized redox homeostasis, even at the cost of perturbed energy metabolism and associated inflammation, was key to survival over longer low pO2 exposure time periods. We also provided indicators in human plasma (alpha-1-antitrypsin, cofilin-1 and S100A8) for cytoskeletal re-arrangements and inflammation. It was observed that innate immune/inflammatory processes were balanced in individuals successfully surviving in low pO2 for extended durations.