Alterations of Human Plasma Proteome Profile on Adaptation to High-Altitude Hypobaric Hypoxia

For
individuals migrating to or residing permanently in high-altitude
regions, environmental hypobaric hypoxia is a primary challenge that
induces several physiological or pathological responses. It is well
documented that human beings adapt to hypobaric hypoxia via some protective
mechanisms, such as erythropoiesis and overproduction of hemoglobin;
however, little is known on the alterations of plasma proteome profiles
in accommodation to high-altitude hypobaric hypoxia. In the present
study, we investigated differential plasma proteomes of high altitude
natives and lowland normal controls by a TMT-based proteomic approach.
A total of 818 proteins were identified, of which 137 were differentially
altered. Bioinformatics (including GO, KEGG, protein–protein
interactions, etc.) analysis showed that the differentially altered
proteins were basically involved in complement and coagulation cascades,
antioxidative stress, and glycolysis. Validation results demonstrated
that CCL18, C9, PF4, MPO, and S100A9 were notably up-regulated, and
HRG and F11 were down-regulated in high altitude natives, which were
consistent with TMT-based proteomic results. Our findings highlight
the contributions of complement and coagulation cascades, antioxidative
stress, and glycolysis in acclimatization to hypobaric hypoxia and
provide a foundation for developing potential diagnostic or/and therapeutic
biomarkers for high altitude hypobaric hypoxia-induced diseases.