Serum proteome profiling of plateau acclimatization in men using Olink proteomics approach

Plateau acclimatization involves adaptive changes in the body's neurohumoral regulation and metabolic processes due to hypoxic conditions at high altitudes. This study utilizes Olink targeted proteomics to analyze serum protein expression differences in Han Chinese individuals acclimatized for 6 months-1 year at 4500 and 5300 m altitudes, compared to those residing at sea level. The objective is to elucidate the proteins' roles in tissue and cellular adaptation to hypoxia. We identified 54 metabolism-related differentially expressed proteins (DEPs) in the serum of the high-altitude group versus the sea-level group, comprising 20 significantly upregulated and 34 downregulated proteins. Notably, 2 proteins were upregulated and 11 downregulated at both 4500 and 5300 m altitudes. The top three protein correlations among DEPs included CRKL with CA13, RNASE3 with NADK, and NADK with APEX1, alongside APLP1 with CTSH, CTSH with SOST, and CTSH with NT-proBNP in inverse correlations. KEGG enrichment analysis indicated significant DEP involvement in various metabolic pathways, particularly those associated with hypoxic cellular metabolism like glycolysis/gluconeogenesis and the HIF-1 signaling pathway. Correlation with clinical phenotypes showed positive associations of SOST, RNASE3, CA13, NADK, and CRKL with SaO₂ and negative correlations with Hemoglobin and Hematocrit; ALDH1A1 positively correlated with Triglyceride; and SDC4 inversely correlated with Uric acid levels. This study provides insights into specific DEPs linked to metabolic adaptations in high-altitude acclimatized individuals, offering a foundation for understanding acclimatization mechanisms and potential therapeutic targets.