Serum vascular endothelial growth factor is a potential biomarker for acute mountain sickness

Abstract

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS.Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1).Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p < 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p < 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p < 0.049, interaction effect).Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS.

Lactobacillus delbrueckii subsp. bulgaricus Alleviates Acute Injury in Hypoxic Mice

“…In hypoxic environments, the body releases EPO to cope with the stress caused by hypoxia [40]. Vascular endothelial growth factor (VEGF) is an effective angiogenic and permeability factor, and studies have demonstrated that low-pressure hypoxic exposure can lead to an increase in VEGF levels in individual serum [41]. Hypoxia-inducible factor-1α (HIF-1α) is the active subunit of hypoxia-inducible factor-1 (HIF-1) and is regulated by hypoxia; under hypoxic conditions, HIF-1α levels in the body significantly increase [42].…”

Potential therapeutic effects of traditional Chinese medicine in acute mountain sickness: pathogenesis, mechanisms and future directions

“…Our team’s previous study found that polysaccharide extracted from Potentilla anserina L could inhibit oxidative stress and inflammatory responses to treat and prevent HACE and HAPE, and its mechanism of action may be to block the activation of the NF-κB and HIF-1α signaling pathways, which inhibits the production of downstream pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and VEGF) ( Shi et al, 2019 ; Shi et al, 2019 ). Meanwhile, Pan Y et al showed that tetrahydrocurcumin significantly reduced the expression of VEGF (AMS biomarker), MMP-9 and NF-κB, and effectively attenuated cerebral edema and inflammation induced by acute high-altitude hypobaric hypoxia ( Pan et al, 2020 ; Nourkami-Tutdibi et al, 2023 ). Moreover, Zha et al established an animal model of AMS (6000 m, 10 m/s rate of ascent, continuous exposure to hypoxia for 24 h) and found that ginsenoside Rg1 reduced the wet-to-dry ratio of lung tissues, improved the pathological changes of lung tissues, decreased the MDA content and NOS viability, elevated the CAT and Na + -K + -ATPase viability, and decreased the IL-6 and TNF-α levels ( Arriaza et al, 2022 ).…”

Recent advances in predicting acute mountain sickness: from multidimensional cohort studies to cutting-edge model applications

“…The N Nourkami-Tutdibi team ( Nourkami-Tutdibi et al, 2023 ) investigated changes in cytokine concentrations in blood samples and their possible association with AMS development. They discovered that VEGF levels significantly increased shortly after high-altitude exposure in AMS patients, suggesting it might be a crucial biomarker for AMS.…”