Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes

Autor: 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, Andrew J. Currie, Tobias R. Kollmann, Nelly Amenyogbe, Amy H. Lee
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-62195-9
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje