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

Sci Rep. 2017 Oct 26;7(1):14143. doi: 10.1038/s41598-017-14396-8.

Abstract

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 O2 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 O2 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 O2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Adhesion
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Female
  • Hindlimb / blood supply*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hyperoxia / physiopathology*
  • Ischemia / physiopathology*
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / physiology*
  • Oxygen / adverse effects
  • Regional Blood Flow
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Oxygen

Grants and funding