Hypobaric hypoxia modulated structural characteristics of circulating cell-free DNA in high-altitude pulmonary edema
The utility of cell-free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for using its full potential. The high-altitude (HA; altitude > 2,500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in patients with high-altitude pulmonary edema (HAPE) (number of subjects, n = 112) and healthy HA sojourners (n = 111). The present study investigated cfDNA characteristics such as concentration, fragment length size, degree of integrity, and subfractions reflecting mitochondrial-cfDNA copies in the two groups. The total cfDNA level was significantly higher in patients with HAPE, and the level increased with increasing HAPE severity (P = 0.0036). A lower degree of cfDNA integrity of 0.346 in patients with HAPE (P = 0.001) indicated the prevalence of shorter cfDNA fragments in circulation in patients compared with the healthy HA sojourners. A significant correlation of cfDNA characteristics with the peripheral oxygen saturation levels in the patient group demonstrated the translational relevance of cfDNA molecules. The correlation was further supported by multivariate logistic regression and receiver operating characteristic curve. To our knowledge, our study is the first to highlight the association of higher cfDNA concentration, a lower degree of cfDNA integrity, and increased mitochondrial-derived cfDNA population with HAPE disease severity. Further deep profiling of cfDNA fragments, which preserves cell-type specific genetic and epigenetic features, can provide dynamic physiological responses to hypoxia.NEW & NOTEWORTHY This study observed altered cell-free (cf) DNA fragment patterns in patients with high-altitude pulmonary edema and the significant correlation of these patterns with peripheral oxygen saturation levels. This suggests deep profiling of cfDNA fragments in the future may identify genetic and epigenetic mechanisms underlying physiological and pathophysiological responses to hypoxia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:326 |
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| Enthalten in: |
American journal of physiology. Lung cellular and molecular physiology - 326(2024), 4 vom: 01. Apr., Seite L496-L507 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ali, Manzoor [VerfasserIn] |
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| Links: |
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| Themen: |
9007-49-2 |
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| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1152/ajplung.00245.2023 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The utility of cell-free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for using its full potential. The high-altitude (HA; altitude > 2,500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in patients with high-altitude pulmonary edema (HAPE) (number of subjects, n = 112) and healthy HA sojourners (n = 111). The present study investigated cfDNA characteristics such as concentration, fragment length size, degree of integrity, and subfractions reflecting mitochondrial-cfDNA copies in the two groups. The total cfDNA level was significantly higher in patients with HAPE, and the level increased with increasing HAPE severity (P = 0.0036). A lower degree of cfDNA integrity of 0.346 in patients with HAPE (P = 0.001) indicated the prevalence of shorter cfDNA fragments in circulation in patients compared with the healthy HA sojourners. A significant correlation of cfDNA characteristics with the peripheral oxygen saturation levels in the patient group demonstrated the translational relevance of cfDNA molecules. The correlation was further supported by multivariate logistic regression and receiver operating characteristic curve. To our knowledge, our study is the first to highlight the association of higher cfDNA concentration, a lower degree of cfDNA integrity, and increased mitochondrial-derived cfDNA population with HAPE disease severity. Further deep profiling of cfDNA fragments, which preserves cell-type specific genetic and epigenetic features, can provide dynamic physiological responses to hypoxia.NEW & NOTEWORTHY This study observed altered cell-free (cf) DNA fragment patterns in patients with high-altitude pulmonary edema and the significant correlation of these patterns with peripheral oxygen saturation levels. This suggests deep profiling of cfDNA fragments in the future may identify genetic and epigenetic mechanisms underlying physiological and pathophysiological responses to hypoxia | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a hypobaric hypoxia | |
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| 700 | 1 | |a Mishra, Aastha |e verfasserin |4 aut | |
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