Progress in Mass Spectrometry-Based Proteomics in Hypoxia-Related Diseases and High-Altitude Medicine

Human migration, influenced by social conflict and natural disasters as well as global climate change, has become recognized as a major "planetary force." It has also brought to the forefront, new specialties of integrative biology-such as high-altitude medicine-and the impact of hitherto understudied environmental factors on human pathophysiology in these new geographical settings. For people migrating to or living in high-altitude regions, environmental hypoxia is a primary challenge. Decreased partial pressure of oxygen in environmental air, caused by lower barometric pressure, puts living organisms in a hypoxic state. When there is a serious inability to adapt, death may ensue. Research efforts over the past few years have applied mass spectrometry-based proteomics analyses to uncover the mechanisms of hypoxia-related high-altitude pathophysiology. The differential proteomic profiles in plasma and tissues under high-altitude hypoxia conditions, as compared with sea level controls, and the multitudinous hypoxia-specific proteins identified elucidate mechanisms underlying high-altitude hypoxia acclimatization and diseases, and provide a foundation for development of new therapeutic, prophylactic, and diagnostic approaches. In this expert review and innovation analysis, we highlight the current proteomics findings on high-altitude hypoxia, and suggest paths forward toward effective interventions to address this key challenge in high-altitude medicine.