دورية أكاديمية
Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes
| العنوان: | Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes |
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| المؤلفون: | Fidanza, Mario, Hibbert, Julie, Acton, Erica, Harbeson, Danny, Schoeman, Elizna, Skut, Patrycja, Woodman, Tabitha, Eynaud, Adrien, Hartnell, Lucy, Brook, Byron, Cai, Bing, Lo, Mandy, Falsafi, Reza, Hancock, Robert E W, Chiume-Kayuni, Msandeni, Lufesi, Norman, Popescu, Constantin R, Lavoie, Pascal M, Strunk, Tobias, Kollmann, Tobias R, Currie, Andrew J, Amenyogbe, Nelly, Lee, Amy H |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Angiogenesis, Angiopoietin-1 - blood, Angiopoietin-1 - metabolism, Animals, Newborn, Arachidonic Acid - blood, Arachidonic Acid - metabolism, Arginine - blood, Arginine - metabolism, Biomarkers - blood, Disease Models, Animal, Female, Humans, Infant, Male, Mice, Neonatal Sepsis, Neovascularization, Pathologic - metabolism, Nitric Oxide - blood, Nitric Oxide - metabolism, Nitric Oxide Synthase Type III - metabolism, Reactive Oxygen Species - metabolism, Signal Transduction |
| الوصف: | Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here provide the mechanistic evidence in support of the relevance for these observations. Angiopoetin-1 (Ang-1), which promotes vascular integrity, was decreased in blood plasma of human and murine septic newborns. In preclinical models, administration of Ang-1 provided prophylactic protection from septic death. Arachidonic acid metabolism appears to be functionally connected to Ang-1 via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Strengthening this intersection via oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death while also increasing plasma Ang-1 levels among septic newborns. Our data highlight that targeting angiogenesis-associated pathways with interventions that increase Ang-1 activity directly or indirectly through ROS/eNOS provide promising avenues to prevent and/or treat severe neonatal sepsis. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | ispartof: Scientific reports vol 14; 991005666667607891; https://researchportal.murdoch.edu.au/esploro/outputs/journalArticle/Angiogenesis-associated-pathways-play-critical-roles-in/991005666667607891Test; https://researchportal.murdoch.edu.au/view/delivery/61MUN_INST/12162685070007891/13162685060007891Test; alma:61MUN_INST/bibs/991005666667607891 |
| DOI: | 10.1038/s41598-024-62195-9 |
| الإتاحة: | https://doi.org/10.1038/s41598-024-62195-9Test https://researchportal.murdoch.edu.au/esploro/outputs/journalArticle/Angiogenesis-associated-pathways-play-critical-roles-in/991005666667607891Test https://researchportal.murdoch.edu.au/view/delivery/61MUN_INST/12162685070007891/13162685060007891Test |
| حقوق: | © The Author(s) 2024 ; Open ; CC BY V4.0 |
| رقم الانضمام: | edsbas.FCFF6902 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-024-62195-9 |