Differences in Tolerance to Hypoxia: Physiological, Biochemical, and Molecular-Biological Characteristics

Abstract

Hypoxia plays an important role in the development of many infectious, inflammatory, and tumor diseases. The predisposition to such disorders is mostly provided by differences in basic tolerance to oxygen deficiency, which we discuss in this review. Except the direct exposure of different-severity hypoxia in decompression chambers or in highland conditions, there are no alternative methods for determining organism tolerance. Due to the variability of the detection methods, differences in many parameters between tolerant and susceptible organisms are still not well-characterized, but some of them can serve as biomarkers of susceptibility to hypoxia. At the moment, several potential biomarkers in conditions after hypoxic exposure have been identified both in experimental animals and humans. The main potential biomarkers are Hypoxia-Inducible Factor (HIF)-1, Heat-Shock Protein 70 (HSP70), and NO. Due to the different mechanisms of various high-altitude diseases, biomarkers may not be highly specific and universal. Therefore, it is extremely important to conduct research on hypoxia susceptibility biomarkers. Moreover, it is important to develop a method for the evaluation of organisms' basic hypoxia tolerance without the necessity of any oxygen deficiency exposure. This can contribute to new personalized medicine approaches' development for diagnostics and the treatment of inflammatory and tumor diseases, taking into account hypoxia tolerance differences.

Keywords: acute mountain sickness; biomarkers; high altitude; high-altitude pulmonary edema; hypoxia-inducible factor; tolerance to hypoxia.

Figure 1

Common biomarkers, revealed both in humans and animals (HIF-1—Hypoxia-Inducible Factor, HSP70—Heat-Shock Protein 70, NO—Nitric Oxide), which are supposed to be responsible for determination of hypoxia tolerance and possible biomarkers, differences in which were demonstrated among humans with different AMS and HAPE tolerance (ANP—Atrial Natriuretic Peptide, BNP—Brain Natriuretic Peptide, Dkk4—Dickkopf WNT signaling pathway inhibitor 4, IGFBP6—Insulin-like Growth Factor Binding Protein 6, IL-1RA—Interleukin 1 Receptor Agonist, IL-17RA—Interleukin 17 Receptor A, MIP-1—Macrophage Inflammatory Protein-1, T₃, SAA1—Serum Amyloid A1).