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 high-altitude pulmonary edema (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 (<i>n</i> = 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 hematological and gene-expression profiles. HR was elevated, and Spo₂ and HRV were significantly reduced in a fraction of inspired oxygen ([Formula: see text])-dependent manner. After exposure to hypoxia, there was a minimal decrease in HCT, red blood cell distribution width (RDW)-coefficient of variation (CV), mean platelet volume (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. Eighty-two genes significantly differed after hypoxia exposure, with 46 upregulated genes and 36 downregulated genes (<i>P</i> ≤ 0.05 and log₂-fold change greater than ±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.<b>NEW & NOTEWORTHY</b> Our study delves into the multifaceted response to hypoxia, integrating gene expression and hematological, biochemical, and physiological assessments. Hypoxia, crucial in both physiology and pathology, prompts varied responses, necessitating a thorough systemic understanding. Examining healthy subjects exposed to graded normobaric hypoxia, we observed significant shifts in heart rate, oxygen saturation, and heart rate variability. Moreover, genomic analysis unveiled distinct gene signatures associated with physiological parameters, offering insights into molecular perturbations and adaptations to oxygen deprivation.