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.
Highlights
Oxygen deficiency is one of the key factors in the development of infectious, inflammatory, and tumor diseases [1,2,3,4,5,6]
In colon cancer associated with a chronic colitis model, it was demonstrated that an increase in Hypoxia-Inducible Factor (HIF)-1 expression in intestinal epithelial cells does not lead to the formation of tumors or further cancer progression, but HIF-2-mediated inflammation contributes to the development of colon tumors, and HIF-2α activation in acute colitis causes severe inflammation [73,74]
We showed an increase in the level of HIF-1 expression in tolerant-to-hypoxia Wistar rats after a single measurement of the resistance to oxygen deficiency, accompanied by an increase in vascular endothelial growth factor (VEGF) and erythropoietin content [194]
Summary
Oxygen deficiency is one of the key factors in the development of infectious, inflammatory, and tumor diseases [1,2,3,4,5,6]. The differences in basic tolerance to oxygen deficiency can determine the predisposition to the development of hypoxia-related disorders The evidence of this fact can serve, for instance, the variations in angiogenic responses to hypoxia, which may alter adaptive changes in coronary artery disease [23]. At present, the physiological, biochemical, and molecular-biological characteristics of hypoxia-tolerant and -susceptible organisms remain not well-studied. The research in this field could result in discovering the possible biomarkers of hypoxia susceptibility. In this review we discuss the physiological, biochemical, and biomolecular characteristics of humans and animals with different tolerances to hypoxia, taking into consideration various methods of their evaluation, as well as possible biomarkers for determining the basic resistance to oxygen deficiency without hypoxic exposure. The study of differences between hypoxia-tolerant and hypoxia-susceptible organisms is relevant for flight and space medicine since oxygen deficiency is a significant risk factor in space flights and extravehicular activities
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