Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han males
Background Altitude acclimatization is a physiological process that restores oxygen delivery to the tissues and promotes oxygen use under high altitude hypoxia. High altitude sickness occurs in individuals without acclimatization. Unraveling the molecular underpinnings of altitude acclimatization co...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00601/full |
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| author | Bao Liu He Huang Shou-Xian Wang Gang Wu Gang Xu Bing-Da Sun Er-Long Zhang Yu-Qi Gao |
| author_facet | Bao Liu He Huang Shou-Xian Wang Gang Wu Gang Xu Bing-Da Sun Er-Long Zhang Yu-Qi Gao |
| author_sort | Bao Liu |
| collection | DOAJ |
| description | Background Altitude acclimatization is a physiological process that restores oxygen delivery to the tissues and promotes oxygen use under high altitude hypoxia. High altitude sickness occurs in individuals without acclimatization. Unraveling the molecular underpinnings of altitude acclimatization could help understand the beneficial body responses to high altitude hypoxia as well as the altered biological events in un-acclimatized individuals. This study assessed physiological adjustments and circulating microRNA (cmiRNA) profiles in individuals exposed to high altitude, aiming to explore altitude acclimatization in humans.MethodsNinety volunteers were enrolled in this study. Among them, 22 individuals provided samples for microRNA arrays; 68 additional individuals constituted the validation set. Un-acclimatized individuals were identified by the Lake Louise Scoring System. Thirty-three phenotypes were recorded pre- and post-exposure to high altitude, including stress hormones, lipid profiles, hematological indices, myocardial enzyme spectrum, and liver and kidney function related enzymes. CmiRNA expression profiles were assessed using miRCURYTM LNA Array (v.18.0) screening, with data validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then, associations of plasma microRNA expression with physiological adjustments were evaluated. The biological relevance of the main differentially expressed cmiRNAs was explored by bioinformatics prediction.ResultsNineteen of the 33 phenotypes were significantly altered during early altitude acclimatization, including hematological indices, lipid profiles, and stress hormones; meanwhile, 86 cmiRNAs (79 up-regulated and 7 down-regulated) showed differential expression with statistical significance. Among them, 32 and 25 microRNAs were strongly correlated with low-density lipoprotein-cholesterol and total cholesterol elevations, respectively. In addition, 22 microRNAs were closely correlated with cortisol increase. In un-acclimatized individuals, 55 cmiRNAs were up-regulated and 36 down-regulated, compared with acclimatized individuals. The HIF signaling pathway was suppressed in un-acclimatized individuals.ConclusionPhysiological adjustments, including the hematological system, stress hormones, and lipid molecules contributed to early altitude acclimatization, and showed strong correlations with cmiRNA reprogramming. Moreover, acclimatized and un-acclimatized individuals showed different cmiRNA profile. Suppression of the HIF-1 signaling pathway by microRNA regulation may play a key role in the pathogenesis of un-acclimatization with high altitude hypoxia. |
| first_indexed | 2024-12-12T22:18:01Z |
| format | Article |
| id | doaj.art-5d7b1143ef56413d8ea087880dbfd53f |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-12T22:18:01Z |
| publishDate | 2016-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-5d7b1143ef56413d8ea087880dbfd53f2022-12-22T00:10:00ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-12-01710.3389/fphys.2016.00601221745Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han malesBao Liu0He Huang1Shou-Xian Wang2Gang Wu3Gang Xu4Bing-Da Sun5Er-Long Zhang6Yu-Qi Gao7Third Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityBackground Altitude acclimatization is a physiological process that restores oxygen delivery to the tissues and promotes oxygen use under high altitude hypoxia. High altitude sickness occurs in individuals without acclimatization. Unraveling the molecular underpinnings of altitude acclimatization could help understand the beneficial body responses to high altitude hypoxia as well as the altered biological events in un-acclimatized individuals. This study assessed physiological adjustments and circulating microRNA (cmiRNA) profiles in individuals exposed to high altitude, aiming to explore altitude acclimatization in humans.MethodsNinety volunteers were enrolled in this study. Among them, 22 individuals provided samples for microRNA arrays; 68 additional individuals constituted the validation set. Un-acclimatized individuals were identified by the Lake Louise Scoring System. Thirty-three phenotypes were recorded pre- and post-exposure to high altitude, including stress hormones, lipid profiles, hematological indices, myocardial enzyme spectrum, and liver and kidney function related enzymes. CmiRNA expression profiles were assessed using miRCURYTM LNA Array (v.18.0) screening, with data validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then, associations of plasma microRNA expression with physiological adjustments were evaluated. The biological relevance of the main differentially expressed cmiRNAs was explored by bioinformatics prediction.ResultsNineteen of the 33 phenotypes were significantly altered during early altitude acclimatization, including hematological indices, lipid profiles, and stress hormones; meanwhile, 86 cmiRNAs (79 up-regulated and 7 down-regulated) showed differential expression with statistical significance. Among them, 32 and 25 microRNAs were strongly correlated with low-density lipoprotein-cholesterol and total cholesterol elevations, respectively. In addition, 22 microRNAs were closely correlated with cortisol increase. In un-acclimatized individuals, 55 cmiRNAs were up-regulated and 36 down-regulated, compared with acclimatized individuals. The HIF signaling pathway was suppressed in un-acclimatized individuals.ConclusionPhysiological adjustments, including the hematological system, stress hormones, and lipid molecules contributed to early altitude acclimatization, and showed strong correlations with cmiRNA reprogramming. Moreover, acclimatized and un-acclimatized individuals showed different cmiRNA profile. Suppression of the HIF-1 signaling pathway by microRNA regulation may play a key role in the pathogenesis of un-acclimatization with high altitude hypoxia.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00601/fullAcclimatizationhypoxiacirculating microRNAshigh altitudeChinese Han males |
| spellingShingle | Bao Liu He Huang Shou-Xian Wang Gang Wu Gang Xu Bing-Da Sun Er-Long Zhang Yu-Qi Gao Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han males Frontiers in Physiology Acclimatization hypoxia circulating microRNAs high altitude Chinese Han males |
| title | Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han males |
| title_full | Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han males |
| title_fullStr | Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han males |
| title_full_unstemmed | Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han males |
| title_short | Physiological adjustments and circulating microRNA reprogramming are involved in early acclimatization to high altitude in Chinese Han males |
| title_sort | physiological adjustments and circulating microrna reprogramming are involved in early acclimatization to high altitude in chinese han males |
| topic | Acclimatization hypoxia circulating microRNAs high altitude Chinese Han males |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00601/full |
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