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.