MicroRNAs and genes regulating responses to hypoxia and inflammation expression levels in blood leukocytes as potential biomarkers of initial oxygen deficiency tolerance

Introduction Hypoxia-inducible factors (HIFs) play central roles in evoking responses to hypoxia, and their activities are regulated by numerous molecules, including microRNAs. Organisms typically show differing tolerances to oxygen deficiency; the most common method of determining such tolerance involves examining the effects of sublethal hypoxic exposure (SHE) in a decompression chamber, which can lead to pathological changes in the internal organs. The aim of the present study was to investigate the microRNAs and genes regulating cellular responses to hypoxia and inflammation expression levels in the peripheral blood leukocytes of laboratory animals before and 1 month following determination of hypoxia tolerance. Methods In animals not exposed to hypoxic exposure, blood was collected from the tail vein. One month later, the rats’ resistance to hypoxia was determined at a critical altitude (11,500 m) in a single test in a decompression chamber, based on the “gasping time” before assuming a lateral position and the appearance of signs of asphyxia. Two groups of rats were identified – tolerant and susceptible to hypoxia. The expression of mRNA Hif1a , Epas1 , Hif3a , Arnt , Vegf , Epo , Egln1 , Nfkb , Il1b , Tnfa , Tgfb and microRNA rno-miR-210-5p , rno-miR-210-3p , rno-miR-107-5p , rno-miR-107-3p , rno-miR-145-5p , rno-miR-145-3p , rno-miR-155-5p , rno-miR-155-3p in leukocytes was determined by real-time PCR. To assess the impact of SHE on internal organs, morphological and morphometric studies of the lungs were carried out. Results Compared to tolerant rats, the susceptible animals demonstrated an initial high proinflammatory potential characterized by high Hif1a , Epas1 , Hif3a , and Nfkb expression along with low levels of rno-miR-155-3p and rno-miR-210-3p in the leukocytes. We observed the activation of proinflammatory responses in both tolerant and susceptible animals, and additional expression level increases of Il1b and Tnfa were noted only in the susceptible rats. Discussion SHE has extended effects on organisms that last for at least a month. The indicators identified herein, which differ between the hypoxia-tolerant and hypoxia-susceptible animals before sublethal hypoxic exposure, can therefore be considered as biomarkers of the initial hypoxia tolerance potential.