PMID- 29075011
OWN - NLM
STAT- MEDLINE
DCOM- 20190716
LR  - 20190716
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Oct 26
TI  - Neonatal exposure to high oxygen levels leads to impaired ischemia-induced 
      neovascularization in adulthood.
PG  - 14143
LID - 10.1038/s41598-017-14396-8 [doi]
LID - 14143
AB  - 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.
FAU - Mathieu, Raphael
AU  - Mathieu R
AD  - Department of Medicine, Centre Hospitalier de l'Universite de Montreal (CHUM) 
      Research Center, Montreal, Quebec, Canada.
FAU - Dussault, Sylvie
AU  - Dussault S
AD  - Department of Medicine, Centre Hospitalier de l'Universite de Montreal (CHUM) 
      Research Center, Montreal, Quebec, Canada.
FAU - Desjarlais, Michel
AU  - Desjarlais M
AD  - Department of Medicine, Centre Hospitalier de l'Universite de Montreal (CHUM) 
      Research Center, Montreal, Quebec, Canada.
FAU - Rivard, Francois
AU  - Rivard F
AD  - Department of Medicine, Centre Hospitalier de l'Universite de Montreal (CHUM) 
      Research Center, Montreal, Quebec, Canada.
FAU - Dhahri, Wahiba
AU  - Dhahri W
AD  - Department of Medicine, Centre Hospitalier de l'Universite de Montreal (CHUM) 
      Research Center, Montreal, Quebec, Canada.
FAU - Cloutier, Anik
AU  - Cloutier A
AD  - Department of Pediatrics, Sainte-Justine University Hospital Research Center, 
      Montreal, Quebec, Canada.
FAU - Nuyt, Anne-Monique
AU  - Nuyt AM
AD  - Department of Pediatrics, Sainte-Justine University Hospital Research Center, 
      Montreal, Quebec, Canada.
FAU - Rivard, Alain
AU  - Rivard A
AD  - Department of Medicine, Centre Hospitalier de l'Universite de Montreal (CHUM) 
      Research Center, Montreal, Quebec, Canada. alain.rivard@umontreal.ca.
LA  - eng
GR  - MOP-123490/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171026
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Adhesion
MH  - Disease Models, Animal
MH  - Endothelial Cells/cytology/physiology
MH  - Female
MH  - Hindlimb/*blood supply
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Hyperoxia/*physiopathology
MH  - Ischemia/*physiopathology
MH  - Mice, Inbred C57BL
MH  - Neovascularization, Physiologic/*physiology
MH  - Oxygen/adverse effects
MH  - Regional Blood Flow
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC5658429
COIS- The authors declare that they have no competing interests.
EDAT- 2017/10/28 06:00
MHDA- 2019/07/17 06:00
PMCR- 2017/10/26
CRDT- 2017/10/28 06:00
PHST- 2017/04/13 00:00 [received]
PHST- 2017/10/10 00:00 [accepted]
PHST- 2017/10/28 06:00 [entrez]
PHST- 2017/10/28 06:00 [pubmed]
PHST- 2019/07/17 06:00 [medline]
PHST- 2017/10/26 00:00 [pmc-release]
AID - 10.1038/s41598-017-14396-8 [pii]
AID - 14396 [pii]
AID - 10.1038/s41598-017-14396-8 [doi]
PST - epublish
SO  - Sci Rep. 2017 Oct 26;7(1):14143. doi: 10.1038/s41598-017-14396-8.