Physiological, biochemical and genome-wide expression patterns during graded normobaric hypoxia in healthy individuals

The regulation of oxygen homeostasis is critical in physiology and disease pathogenesis. High Altitude environment or hypoxia (lack of oxygen) can lead to adverse health conditions such as HAPE despite initial adaptive physiological responses. Studying genetic, hematological and biochemical, and the physiological outcomes of hypoxia together could yield a comprehensive understanding and potentially uncover valuable biomarkers for predicting responses. To this end, healthy individuals (n=51) were recruited and exposed to graded normobaric hypoxia. Physiological parameters such as Heart Rate(HR), Heart Rate Variability(HRV), oxygen saturation(SpO₂), and Blood Pressure(BP) were constantly monitored, and a blood sample was collected before and after the hypoxia exposure for the haematological and gene-expression profiles. HR was elevated, and SpO₂ and HRV were significantly reduced in a FiO₂-dependent manner. After exposure to hypoxia, there was a minimal decrease in HCT, RDW-CV, MPV, Platelet Distribution Width, Plateletcrit, Eosinophils, Lymphocytes and HDL-Cholesterol. Additionally, there was a marginal increase observed in Neutrophils. The effect of hypoxia was further assessed at the genome-wide expression level in a subset of individuals. 82 genes significantly differed after hypoxia exposure, with 46 up-regulated genes and 36 down-regulated genes (p ≤ 0.05 and log₂ fold change > ± 0.5). We also conducted an integrative analysis of global gene expression profiles linked with physiological parameters, and we uncovered numerous reliable gene signatures associated with BP, SpO₂, HR, and HRV in response to graded normobaric hypoxia.