The Effects of Acute Hypoxia on Tissue Oxygenation and Circulating Alarmins in Healthy Adults

Abstract

The binding of high-mobility group box-1 (HMGB-1) to the membrane receptor for advanced glycation end-products (mRAGE) is a key early mediator of non-infectious inflammation and its triggers include ischaemia/hypoxia. The effects of acute hypoxia on soluble RAGE (sRAGE) are unknown. Fourteen healthy adults (50 % women; 26.6±3.8 years) were assessed at baseline normoxia (T0), followed by four time-points (T90, 95, 100 and 180 min) over three hours of continuous normobaric hypoxia (NH, 4,450 m equivalent) and again 60 min after return to normoxia (T240). A 5-min exercise step test was performed during NH at T90. Plasma concentrations of HMGB-1, sRAGE VCAM-1, ICAM-1, VEGF IL-8 and IL-13 were measured using venous blood. Arterial and tissue oxygen saturations were measured using pulse oximetry (SpO2) and near-infrared spectroscopy (StO2), respectively. NH led to a significant reduction in SpO2, StO2, sRAGE and VEGF, which was compounded by exercise, before increasing to baseline values with normoxic restoration (T240). NH-exercise led to a paired increase in HMGB-1. sRAGE inversely correlated with HMGB-1 (r=-0.32; p=0.006), heart rate (r=-0.43; p=0.004) but was not linked to SpO2 or StO2. In conclusion, short-term NH leads to a fall in sRAGE and VEGF concentrations with a transient rise post NH-exercise in HMGB-1.

Concurrent high-intensity aerobic and resistance exercise modulates systemic release of alarmins (HMGB1, S100A8/A9, HSP70) and inflammatory biomarkers in healthy young men: a pilot study

“…Nevertheless, separate findings from these studies show that acute exercise increases circulating alarmins, such as HMGB1, and supports our working hypothesis that strenuous/exhaustive exercise is a "danger" or stressor to the physiological system (13). Systemic HMGB1 increased after strenuous aerobic exercise, including exhaustive treadmill running (14), a half-or full-marathon race (12) and a 5-min step test in a hypoxic chamber (15). Likewise, serum HSP70 increased after a single bout of treadmill running in an ambient environment (20 °C) at an intensity of 70% VO 2 peak for 60 min (16) and also after 2 h of semi-recumbent cycling at ~ 60% VO 2 max (17).…”

Altitude, Exercise, and Skeletal Muscle Angio-Adaptive Responses to Hypoxia: A Complex Story

“…Most of the studies that have assessed VEGF-A expression in the muscle tissue have measured mRNA levels only, whereas the protein was essentially quantified in the plasma or serum by ELISA ( Asano et al, 1998 ; Gunga et al, 1999 , 2003 ; Schobersberger et al, 2000 ; Hanaoka et al, 2003 ; Oltmanns et al, 2006 ; Bahtiyar et al, 2007 ; Dorward et al, 2007 ; Ding et al, 2012 ; Morici et al, 2013 ; Brinkmann et al, 2017 ; Boos et al, 2018 ; Kasai et al, 2019 ; Kasperska and Zembron-Lacny, 2020 ). Results from the literature remain largely inconsistent, reporting some increase in mRNA or protein ( Breen et al, 1996 ; Gavin et al, 2006 ), some attenuation ( Olfert et al, 2001 ; Oltmanns et al, 2006 ; Morici et al, 2013 ; Boos et al, 2018 ), or no change ( Gunga et al, 2003 ; Lundby, 2004 ; Bahtiyar et al, 2007 ). Additionally, circulating VEGF-A levels measured by ELISA do not necessarily reflect skeletal muscle VEGF-A production.…”

Concurrent high-intensity aerobic and resistance exercise modulates systemic release of alarmins (HMGB1, S100A8/A9, HSP70) and inflammatory biomarkers in healthy young men: a pilot study

“…Systemic HMGB1 increased after strenuous aerobic exercise, including exhaustive treadmill running [14], a half-or full-marathon race [12] and a 5-min step test in a hypoxic chamber [15]. Likewise, serum HSP70 increased after a single bout of treadmill running in an ambient environment (20°C) at an intensity of 70% VO 2 peak for 60 min [16] and also after 2 h of semi-recumbent cycling at~60% VO 2 max [17].…”