Molecular and Cellular Mechanisms of Cardiac Adaptation to Hypobaric Hypoxia
Abstract
Objective . To evaluate the dynamics of morphofunctional changes and the expression of hypoxia-induced genes in the rat myocardium at different stages of adaptation to intermittent hypobaric hypoxia. Materials and Methods . The study was conducted on male Wistar rats (n=72). Intermittent hypobaric hypoxia (IHH) was modeled in a pressure chamber simulating an ascent to 6,500 m above sea level (5 min ascent, 10 min at altitude, 5 min descent; 5 cycles, 6 times a week, for 30 days). Blood was collected before and after the cycles to determine gas composition. Stained and cleared histological preparations of the left ventricle were used to determine the number and diameter of muscle fibers and capillaries. The dynamics of HIF1A , NOS3 , VEGFA , and EPOR gene expression were determined by reverse transcription polymerase chain reaction (RT-PCR). Structural and functional changes were assessed in the control group and on days 1, 15, and 30. Results . During intermittent hypobaric hypoxia sessions, arterial blood oxygen tension decreased to 52–57 mm Hg. In the first days, reactive vascular changes were observed, accompanied by a more than 10-fold increase in HIF1A expression. On days 15 and 30, as adaptation to intermittent hypobaric hypoxia progressed, a statistically significant increase in the total capillary count was observed: by 7.5 % and 10.7 %, respectively. At the same time points, a three-fold increase in VEGFA and NOS3 expression was observed, while EPOR increased two-fold on day 30 relative to control values. Conclusion . Intermittent hypobaric hypoxia sessions are accompanied by increased HIF1A gene expression in the myocardium at all stages of month-long adaptation to hypoxia, with simultaneous activation of the NOS3 , EPOR , and VEGFA genes. In the early stages, reactive changes were observed, which, as the duration of hypoxic exposure increased, were replaced by structural remodelling of the capillary bed, indicating improved myocardial blood supply and the formation of structural signs of cardiac adaptation to hypoxia.