Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes

Mario Fidanza; Julie Hibbert; Erica Acton; Danny Harbeson; Elizna Schoeman; Patrycja Skut; Tabitha Woodman; Adrien Eynaud; Lucy Hartnell; Byron Brook; Bing Cai; Mandy Lo; Reza Falsafi; Robert E W Hancock; Msandeni Chiume-Kayuni; Norman Lufesi; Constantin R Popescu; Pascal M Lavoie; Tobias Strunk; Tobias R Kollmann; Andrew J Currie; Nelly Amenyogbe; Amy H Lee

doi:10.1038/s41598-024-62195-9

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Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes

Journal article

Open access

Peer reviewed

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes

Mario Fidanza, Julie Hibbert, Erica Acton, Danny Harbeson, Elizna Schoeman, Patrycja Skut, Tabitha Woodman, Adrien Eynaud, Lucy Hartnell, Byron Brook, …

Scientific reports, Vol.14, 11444

2024

DOI: https://doi.org/10.1038/s41598-024-62195-9

PMID: 38769383

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Abstract

Angiogenesis

Angiopoietin-1 - blood

Angiopoietin-1 - metabolism

Animals

Animals, Newborn

Arachidonic Acid - blood

Arachidonic Acid - metabolism

Arginine - blood

Arginine - metabolism

Biomarkers - blood

Disease Models, Animal

Female

Humans

Infant, Newborn

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

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 Australia
Julie Hibbert - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Erica Acton - Simon Fraser University
Danny Harbeson - University of British Columbia
Elizna Schoeman - The Kids Research Institute Australia
Patrycja Skut - The Kids Research Institute Australia
Tabitha Woodman - Murdoch University
Adrien Eynaud - The Kids Research Institute Australia
Lucy Hartnell - The Kids Research Institute Australia
Byron Brook - University of British Columbia
Bing Cai - University of British Columbia
Mandy Lo - University of British Columbia
Reza Falsafi - University of British Columbia
Robert E W Hancock - University of British Columbia
Msandeni Chiume-Kayuni - Kamuzu Central Hospital
Norman Lufesi - Ministry of Health
Constantin R Popescu - University of British Columbia
Pascal M Lavoie - University of British Columbia
Tobias Strunk - The Kids Research Institute Australia
Tobias R Kollmann - Dalhousie University
Andrew J Currie - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Nelly Amenyogbe - Dalhousie University
Amy H Lee - BC Children's Hospital
Publication Details: Scientific reports, Vol.14, 11444
Publisher: Springer Nature
Identifiers: 991005666667607891
Murdoch Affiliation: School of Medical, Molecular and Forensic Sciences
Language: English
Resource Type: Journal article

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