Integration of Metabolomics and Proteomics Reveals the Molecular Characterization of High-Altitude Hyperuricemia

Hypobaric hypoxia-induced hyperuricemia (HUA) is a major health challenge for high-altitude populations, yet its molecular mechanisms remain poorly understood. This study employed metabolomic and proteomic profiling of a high-altitude cohort (10 HUA patients and 10 matched controls) to address this gap. HUA patients exhibited significantly elevated uric acid (UA), creatine kinase, and lactate dehydrogenase levels alongside reduced platelet counts. Metabolomic analysis identified 79 significantly altered metabolites, which were associated with amino acids, lipids, and other pathways, including glycerophospholipid and riboflavin metabolism. Notably, l-cystathionine and serine emerged as potential discriminatory biomarkers for HUA. Parallel proteomics revealed 46 differentially expressed proteins, predominantly linked to complement activation and immune response pathways. Functional enrichment analysis indicated upregulated immune signaling and downregulated hemostasis-related proteins in HUA patients. A machine learning model identified 30 molecular signatures, including both proteins and metabolites, that could distinguish HUA from the control subjects. The resulting signature demonstrated a high discriminatory power. Furthermore, protein-metabolite interaction networks unveiled key regulators and potential therapeutic targets for HUA. These findings provide novel insights into the underlying molecular mechanisms of high-altitude HUA and highlight potential diagnostic and therapeutic strategies for hypobaric hypoxia conditions.