Neonatal exposure to high oxygen levels leads to impaired ischemia-induced neovascularization in adulthood

Adverse perinatal conditions can lead to developmental programming of cardiovascular diseases. Prematurely born infants are often exposed to high oxygen levels, which in animal models has been associated with endothelial dysfunction, hypertension, and cardiac remodeling during adulthood. Here we fou...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-10, Vol.7 (1), p.14143-10, Article 14143
Main Authors: Mathieu, Raphael, Dussault, Sylvie, Desjarlais, Michel, Rivard, François, Dhahri, Wahiba, Cloutier, Anik, Nuyt, Anne-Monique, Rivard, Alain
Format: Article
Language:English
Subjects:
13
59
631/443/1338/16
64/60
692/699/75/593/1920
82/80
Angiogenesis
Animal models
Aorta
Birth
Blood flow
Cardiovascular diseases
Endothelial cells
Heart diseases
Humanities and Social Sciences
Hyperoxia
Hypertension
Infants
Ischemia
multidisciplinary
Muscles
Neonates
Oxidative stress
Oxygen
Rodents
Science
Science (multidisciplinary)
Superoxide dismutase
Vascular endothelial growth factor
Vascularization
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Adverse perinatal conditions can lead to developmental programming of cardiovascular diseases. Prematurely born infants are often exposed to high oxygen levels, which in animal models has been associated with endothelial dysfunction, hypertension, and cardiac remodeling during adulthood. Here we found that adult mice that have been transiently exposed to O 2 after birth show defective neovasculariation after hindlimb ischemia, as demonstrated by impaired blood flow recovery, reduced vascular density in ischemic muscles and increased tissue damages. Ischemic muscles isolated from mice exposed to O 2 after birth exhibit increased oxidative stress levels and reduced expression of superoxide dismutase 1 (SOD1) and vascular endothelial growth factor (VEGF). Pro-angiogenic cells (PACs) have been shown to have an important role for postnatal neovascularisation. We found that neonatal exposure to O 2 is associated with reduced number of PACs in adults. Moreover, the angiogenic activities of both PACs and mature mouse aortic endothelial cells (MAECs) are significantly impaired in mice exposed to hyperoxia after birth. Our results indicate that neonatal exposure to high oxygen levels leads to impaired ischemia-induced neovascularization during adulthood. The mechanism involves deleterious effects on oxidative stress levels and angiogenic signals in ischemic muscles, together with dysfunctional activities of PACs and mature endothelial cells.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-14396-8