The Response Of Plasma Hypoxia-inducible Factor-1 Alpha, Serum Erythropoietin And Plasma Vascular Endothelial Growth Factor During Acute Exposure To Altitude (4300 M)

Abstract

The response of plasma hypoxia-inducible factor-1 alpha, serum erythropoietin and plasma vascular endothelial growth factor during acute exposure to altitude (4300 m) Salgado, R.M.1 and Beidleman, B.A.2 1Thermal and Mountain Medicine Division, US Army Research Institute of Environmental Medicine, Natick, MA 2Biophysics and Biomedical Modeling Division, US Army Research Institute of Environmental Medicine, Natick, MA Intracellular hypoxia-inducible factor-1 alpha (HIF-1α) increases in response to hypoxia and regulates erythropoietin (EPO) and vascular endothelial growth factor (VEGF) expression. However, the response of extracellular HIF-1α (i.e. plasma HIF-1α) to acute hypobaric hypoxia (HH) exposure is unclear. PURPOSE: To determine whether plasma HIF-1α and downstream targets such as serum EPO and plasma VEGF increase from sea level (SL) to acute HH. METHODS: Venous blood samples from 14 SL residents (M = 10, F = 4, age = 23 ± 7 years, ht: 179 ± 10 cm, wt: 74 ± 12 kg, 46 ± 6 ml/kg/min; mean ± SD) were collected after ~20 min of seated rest at SL (~50 m, Natick, MA) and after ~19 hrs of exposure to HH (4300 m, Pikes Peak, CO). Plasma HIF-1α, serum EPO, and plasma VEGF were measured via ELISA assay. RESULTS: From SL to HH, plasma HIF-1α (SL: 287 ± 108 pg/mL vs HH: 264 ± 128 pg/mL, p = 0.51) and plasma VEGF (SL: 74 ± 55 pg/mL vs HH: 100 ± 87 pg/mL, p = 0.23) did not change. From SL to HH, serum EPO increased (SL: 14 ± 15 mIU/mL vs HH: 62 ± 42 mIU/mL, p <0.0001). CONCLUSION: During the first ~19 hrs of HH exposure plasma HIF-1α and plasma VEGF do not increase, while serum EPO does increase. While we were the first to measure plasma HIF-1α during an acute exposure to HH, our results indicate that extracellular HIF-1α may not represent intracellular HIF-1α response to HH. Disclaimer: Author’s views are not official U.S. Army or DoD policy.