The role of hypoxia related hormones responses in acute mountain sickness susceptibility individuals unaccustomed to high altitude
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ABSTRACT:
SUBMITTER: Fayazi B
PROVIDER: S-EPMC10553285 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:The endothelial PAS domain protein 1 (EPAS1) gene functions to sense the blood oxygen level by regulating the hypoxia-inducible transcription factor pathway, and single nucleotide polymorphisms (SNPs) of EPAS1 have been found to have a strong and positive selection in the adaptation of the native Tibetan highland population to high-altitude hypoxia. The aim of the present study was to investigate the effect of EPAS1 SNPs on the risk of acute mountain sickness (AMS) and the physiological responses to acute high-altitude hypoxia in lowland humans. Three tag SNPs (rs6756667, rs13419896 and rs4953354; minor allele frequency, ≥5%) were selected and genotyped in 603 unrelated Han Chinese men, who had traveled to Lhasa (a high-altitude hypoxia environment) by plane, using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. The data showed that the EPAS1 rs6756667 wild-type GG homozygous genotype was associated with elevated AMS risk compared with the AA and AG genotypes (odds ratio, 1.815; 95% confidence interval, 1.233-2.666; P=0.0023) using the dominant-model analysis. EPAS1 rs6756667 GG genotypes were also associated with higher levels of hemoglobin, red blood cells and hematocrit than those carrying the AG heterozygote during AMS development. These findings indicate that EPAS1 SNPs play a role in the physiological effects of AMS, and these effects could be further evaluated as a therapeutic strategy to control acute hypoxia-related human diseases.
| S-EPMC4533176 | biostudies-literature
Project description:BackgroundThe impact of acute mountain sickness (AMS) on individuals ascending to plateaus, soon after exposure to high altitudes, is well-documented. However, the specific relationship between AMS and alterations in blood parameters remains unclear.MethodsA total of 40 healthy volunteers were recruited. Following their arrival at an altitude of 3,300 m, an AMS questionnaire survey was administered 48 h later. Based on the AMS scores obtained, participants were categorized into three groups: non-AMS, mild AMS, and moderate/severe AMS (encompassing both moderate and severe cases). Blood routine tests were performed on all groups at 3-, 7-, and 30-days post-arrival at the plateau, with blood oxygen saturation tests conducted at 3 and 30 days after rapidly entering the plateau.ResultsIn the current investigation, a total of 40 participants were stratified into non-AMS (n = 24), mild-AMS (n = 8), and moderate/severe-AMS (n = 8) cohorts subsequent to rapid ascension to an altitude of 3,300 m. The incidence of AMS in this study was 40%. Noteworthy elevations in red blood cells (RBC), hemoglobin (Hb), and hematocrit (HCT) levels were noted at the 3-day mark post-ascent across all delineated groups. By the 7th day, the moderate/severe-AMS cohort displayed sustained increments in Hb and HCT levels, whereas solely HCT levels rose in the mild-AMS and non-AMS cohorts. Upon reaching the 30-day milestone, the moderate/severe-AMS group demonstrated a reduction in RBC, Hb, and HCT levels, while only HCT levels decreased in the mild-AMS and non-AMS groups. Furthermore, it was observed that all groups exhibited notable reductions in oxygen saturation (SpO2) at 3 days post-ascent, followed by a partial recovery at 30 days, albeit remaining below baseline levels. The correlation analysis results indicated that RBC, Hb, and HCT exhibited a positive correlation with the severity of AMS after a 7-day acclimatization period at high altitude. Conversely, SpO2 demonstrated a negative correlation with the severity of AMS following the same duration at high altitude. The findings of the study suggest a strong association between alterations in RBC, Hb, and HCT levels and AMS, particularly among individuals in the moderate/severe-AMS category who displayed more significant fluctuations in these parameters.ConclusionIndividuals suffering from moderate to severe AMS demonstrated increased levels of RBC, Hb, and HCT, as well as reduced SpO2, indicating a greater need for oxygen adaptation to high-altitude hypoxia. These findings emphasize the physiological adjustments to high altitudes and their potential implications for the treatment of AMS.
| S-EPMC11657198 | biostudies-literature
Project description:BackgroundAscending to high altitude can induce a range of physiological and molecular alterations, rendering a proportion of lowlanders unacclimatized. The prediction of acute mountain sickness (AMS) prior to ascent to high altitude remains elusive.MethodsA total of 40 participants were enrolled for our study in the discovery cohort, and plasma samples were collected from all individuals. The subjects were divided into severe AMS-susceptible (sAMS) group, moderate AMS-susceptible (mAMS) group and non-AMS group based on the Lake Louise Score (LLS) at both 5000m and 3700m. Proteomic analysis was conducted on a cohort of 40 individuals to elucidate differentially expressed proteins (DEPs) and associated pathways between AMS-susceptible group and AMS-resistant group at low altitude (1400m) and middle high-altitude (3700m). Subsequently, a validation cohort consisting of 118 individuals was enrolled. The plasma concentration of selected DEPs were quantified using ELISA. Comparative analyses of DEPs among different groups in validation cohort were performed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the predictive efficiency of DEPs for the occurrence of AMS.ResultsThe occurrence of the AMS symptoms and LLS differed significantly among the three groups in the discovery cohort (p<0.05), as well as in the validation cohort. Comparison of plasma protein profiles using GO analysis revealed that DEPs were primarily enriched in granulocyte activation, neutrophil mediated immunity, and humoral immune response. The comparison of potential biomarkers between the sAMS group and non-AMS group at low altitude revealed statistically higher levels of AAT, SAP and LTF in sAMS group (p=0.01), with a combined area under the curve(AUC) of 0.965. Compared to the mAMS group at low altitude, both SAP and LTF were found to be significantly elevated in the sAMS group, with a combined AUC of 0.887. HSP90-α and SAP exhibited statistically higher levels in the mAMS group compared to the non-AMS group at low altitude, with a combined AUC of 0.874.ConclusionInflammatory and immune related biological processes were significantly different between AMS-susceptible and AMS-resistant groups at low altitude and middle high-altitude. SAP, AAT, LTF and HSP90-α were considered as potential biomarkers at low altitude for the prediction of AMS.
| S-EPMC10569122 | biostudies-literature
Project description:BackgroundAcute mountain sickness (AMS) usually occurs among non-acclimated individuals after rapid ascending to high-altitude environments (generally ≥2,500 m). However, the precise molecular mechanism of AMS remains unclear. Our study aimed to investigate the relationship between several single nucleotide polymorphisms (SNPs) and AMS susceptibility.MethodsIn this work, sequencing data were obtained from 69 AMS patients and 95 matched acclimated Han Chinese individuals from southwest China. Five SNPs (rs1008438, rs150877473, rs1799983, rs2153364, and rs3025039) were systematically investigated in all the participants.ResultsIn our study, we found that allele frequencies of "A" (AMS 69.57% vs. non-AMS 54.74%) and "C" (AMS 30.43% vs. non-AMS 45.26%) in the HSPA1A gene rs1008438 were significantly different between the AMS and non-AMS groups (p = .01). Genotypes "CC" and "CA" of the HSPA1A gene (rs1008438) were associated with lower risk of developing AMS than the genotype "AA." Comparing the genotypes "CC + CA" and "AA," we also observed that the "CC + CA" genotype of rs1008438 was associated with lower AMS risk.ConclusionsIn our case-control study, there was a significant association between the rs1008348 polymorphism and AMS susceptibility, suggesting that this particular SNP might be a Han-specific risk factor for AMS. We believe that this study establishes a foundation for further elucidation of the genetic mechanisms underlying AMS.
| S-EPMC7434611 | biostudies-literature
Project description:Talks, Benjamin James, Catherine Campbell, Stephanie J. Larcombe, Lucy Marlow, Sarah L. Finnegan, Christopher T. Lewis, Samuel J.E. Lucas, Olivia K. Harrison, and Kyle T.S. Pattinson. Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude. High Alt Med Biol. 23:69-77, 2022. Background: Interoception refers to an individual's ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesized that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods: Two groups of 18 participants were recruited to complete a respiratory interoceptive task three times at 2-week intervals. The control group remained in Birmingham (140 m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2,624 m, and test 3 at 2,728 m after an 11-day trek at high altitude (up to 4,800 m). Results: By measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea level measures of anxiety, agoraphobia, and neuroticism. Conclusions: This suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike.
| S-EPMC8982137 | biostudies-literature
Project description:Although extensive studies have focused on the development of acute mountain sickness (AMS), the exact mechanisms of AMS are still obscure. In this study, we used isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis to identify novel AMS-associated biomarkers in human plasma. After 9 hours of hypobaric hypoxia the abundance of proteins related to tricarboxylic acid (TCA) cycle, glycolysis, ribosome, and proteasome were significantly reduced in AMS resistant (AMS-) group, but not in AMS susceptible (AMS+) group. This suggested that AMS- individuals could reduce oxygen consumption via repressing TCA cycle and glycolysis, and reduce energy consumption through decreasing protein degradation and synthesis compared to AMS+ individuals after acute hypoxic exposure. The inflammatory response might be decreased resulting from the repressed TCA cycle. We propose that the ability for oxygen consumption reduction may play an important role in the development of AMS. Our present plasma proteomic study in plateau of the Han Chinese volunteers gives new data to address the development of AMS and potential AMS correlative biomarkers.
| S-EPMC5775437 | biostudies-literature
Project description:Acute mountain sickness (AMS) is a common disabling condition in individuals experiencing high altitudes, which may progress to life-threatening high altitude cerebral edema. Today, no established biomarkers are available for prediction of AMS and Non-AMS individuals before exposure to high altitude.MicroRNAs emerge as promising sensitive and specific biomarkers for a variety of diseases. Thus, we sought to identify circulating microRNAs suitable for prediction the susceptible of AMS before exposure to high altitude. A total of 31 microRNAs were differentially expressed between AMS and Non-AMS groups, 15 up-regulated and 16 down-regulated. Up-regulation of miR-369-3p, miR-449b-3p, miR-136-3p, and miR-4791 in patients with AMS compared with Non-AMS individuals were quantitatively confirmed using qPCR (all, P < 0.001). A unique signature encompassing miR-369-3p, miR-449b-3p, and miR-136-3p discriminate AMS from Non-AMS (area under the curve 0.986, 95%CI 0.970-1.000, P < 0.001, LR+: 14.21, LR-: 0.08). This signature yielded a 92.68% sensitivity and a 93.48% specificity for AMS vs. Non-AMS.The study here, for the first time, describes a signature of three circulating microRNAs as a robust biomarker to differentiate AMS from Non-AMS individuals.
2017-06-10 | GSE90500 | GEO
Project description:BACKGROUND: Each year, thousands of pilgrims travel to the Janai Purnima festival in Gosainkunda, Nepal (4380 m), ascending rapidly and often without the aid of pharmaceutical prophylaxis. METHODS: During the 2012 Janai Purnima festival, 538 subjects were recruited in Dhunche (1950 m) before ascending to Gosainkunda. Through interviews, subjects provided demographic information, ratings of AMS symptoms (Lake Louise Scores; LLS), ascent profiles, and strategies for prophylaxis. RESULTS: In the 491 subjects (91% follow-up rate) who were assessed upon arrival at Gosainkunda, the incidence of AMS was 34.0%. AMS was more common in females than in males (RR?=?1.57; 95% CI?=?1.23, 2.00), and the AMS incidence was greater in subjects >35 years compared to subjects ?35 years (RR?=?1.63; 95% CI?=?1.36, 1.95). There was a greater incidence of AMS in subjects who chose to use garlic as a prophylactic compared to those who did not (RR?=?1.69; 95% CI?=?1.26, 2.28). Although the LLS of brothers had a moderate correlation (intraclass correlation?=?0.40, p?=?0.023), sibling AMS status was a weak predictor of AMS. CONCLUSIONS: The incidence of AMS upon reaching 4380 m was 34% in a large population of Nepalese pilgrims. Sex, age, and ascent rate were significant factors in the development of AMS, and traditional Nepalese remedies were ineffective in the prevention of AMS.
| S-EPMC3794000 | biostudies-other
Project description:Background: Acute mountain sickness (AMS) is a common disabling condition in individuals experiencing high altitudes, which may progress to life-threatening high altitude cerebral edema. Today, no established biomarkers are available for prediction the susceptibility of AMS. MicroRNAs emerge as promising sensitive and specific biomarkers for a variety of diseases. Thus, we sought to identify circulating microRNAs suitable for prediction the susceptible of AMS before exposure to high altitude. Methods: We enrolled 109 healthy man adults and collected blood samples before their exposure to high altitude. Then we took them to an elevation of 3648 m for 5 days. Circulating microRNAs expression was measured by microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). AMS was defined as Lake Louise score ≥3 and headache using Lake Louise Acute Mountain Sickness Scoring System. Results: A total of 31 microRNAs were differentially expressed between AMS and Non-AMS groups, 15 up-regulated and 16 down-regulated. Up-regulation of miR-369-3p, miR-449b-3p, miR-136-3p, and miR-4791 in patients with AMS compared with Non-AMS individuals were quantitatively confirmed using qRT-PCR (all, P < 0.001). With multiple logistic regression analysis, a unique signature encompassing miR-369-3p, miR-449b-3p, and miR-136-3p discriminate AMS from Non-AMS (area under the curve 0.986, 95%CI 0.970-1.000, P < 0.001, LR+: 14.21, LR-: 0.08). This signature yielded a 92.68% sensitivity and a 93.48% specificity for AMS vs. Non-AMS. Conclusion: The study here, for the first time, describes a signature of three circulating microRNAs as a robust biomarker to predict the susceptibility of AMS before exposure to high altitude.
| S-EPMC5296306 | biostudies-literature
Project description:BackgroundThe study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study.Methodology/principal findingsA confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO₂) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO₂ or HR.Conclusions/significanceExposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO₂ and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS.
| S-EPMC3206056 | biostudies-literature