Background & Objectives: Both exercise and hypoxia acutely elicit changes in systemic growth factors and cytokines that mediate increases in erythropoiesis, angiogenesis and, perhaps, arteriogenesis. To what extent the down-stream responses to these interventions are inter-related is, as yet, unclear. A role for circulating micro RNAs (cmiRNAs) in the regulation of these processes is a novel prospect. Thus the aims of this study are to investigate the effect of hypoxia and exercise training on relevant growth factors and cmiRNAs in a healthy human cohort. Methods: 18 healthy, Caucasian, male, elite athletes participated in this study. The project was designed as a parallel, two-groups, matched, randomized, longitudinal (pre-, mid-, post-test), two week intervention. One group was exposed to hypoxia (15 hours/day) the other stayed in a normoxic environment. Both groups performed physical exercise in a 10°C hotter environment than usual. The exercise was standardized for both groups and the daily work load was monitored. Blood was sampled under fasting conditions in the morning, to avoid any effects of acute exercise. Hemoglobin (Hb), reticulocytes, erythropoietin, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), cmiRNAs 144, 146a, 221, 222 were tested in blood and sera. Results: In the normoxic group decreases from pre- to mid- and post-test were found for Hb (p=0.011, p=0.002) and IL-6 (p=0.028, p=0.008). However, in the hypoxic group several changes were apparent. In this group Hb changed at the pre- to mid-test (p=0.013), reticulocytes also increased from pre- to mid-test (p=0.066), erythropoietin increased from pre- to mid- and post-test (p=0.008, p=0.008). VEGF also showed a tendency to increase from pre- to mid-test (p=0.085) and increased from pre- to post-test (p=0.011). The 2-ΔΔCT values for cmiRNAs 221 and 222 showed an increasing trend at the post-test time point but did not reach statistical significance. Conclusions: Hypoxia stimulated several cytokines and growth factors mediating erythropoiesis and angiogenesis, which might have counteracted the plasma volume related decrease in Hb in the normoxic group. While there were changes in cmiRNAs (221 and 222) these were not statistically significant, perhaps due the small study cohort, which is currently being expanded to confirm these results.


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