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Journal article
Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes
Scientific reports, Vol.14, 11444
2024
PMID: 38769383
Abstract
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.
Details
- Title
- Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes
- Authors/Creators
- Mario Fidanza - The Kids Research Institute AustraliaJulie Hibbert - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsErica Acton - Simon Fraser UniversityDanny Harbeson - University of British ColumbiaElizna Schoeman - The Kids Research Institute AustraliaPatrycja Skut - The Kids Research Institute AustraliaTabitha Woodman - Murdoch UniversityAdrien Eynaud - The Kids Research Institute AustraliaLucy Hartnell - The Kids Research Institute AustraliaByron Brook - University of British ColumbiaBing Cai - University of British ColumbiaMandy Lo - University of British ColumbiaReza Falsafi - University of British ColumbiaRobert E W Hancock - University of British ColumbiaMsandeni Chiume-Kayuni - Kamuzu Central HospitalNorman Lufesi - Ministry of HealthConstantin R Popescu - University of British ColumbiaPascal M Lavoie - University of British ColumbiaTobias Strunk - The Kids Research Institute AustraliaTobias R Kollmann - Dalhousie UniversityAndrew J Currie - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsNelly Amenyogbe - Dalhousie UniversityAmy H Lee - BC Children's Hospital
- Publication Details
- Scientific reports, Vol.14, 11444
- Publisher
- Springer Nature
- Identifiers
- 991005666667607891
- Copyright
- © The Author(s) 2024
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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