Logo image
Back
Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs
Journal article   Open access   Peer reviewed

Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs

Mansoor A Syed, Rayman Choo-Wing, Robert J Homer and Vineet Bhandari
PloS one, v 11(1), pp e0147588-e0147588
2016
DOI: https://doi.org/10.1371/journal.pone.0147588
PMID: 26799210
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1371/journal.pone.0147588View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals Animals, Newborn - growth & development Blood Vessels - growth & development Blood Vessels - metabolism Female Lung - growth & development Lung - metabolism Lung Injury - etiology Lung Injury - metabolism Male Mice Mice, Knockout Nitric Oxide Synthase - metabolism Nitric Oxide Synthase - physiology Nitric Oxide Synthase Type I - metabolism Nitric Oxide Synthase Type I - physiology Nitric Oxide Synthase Type II - metabolism Nitric Oxide Synthase Type II - physiology Protein Isoforms - metabolism Vascular Endothelial Growth Factor A - physiology
The role of vascular endothelial growth factor (VEGF)-induced 3 different nitric oxide synthase (NOS) isoforms in lung development and injury in the newborn (NB) lung are not known. We hypothesized that VEGF-induced specific NOS pathways are critical regulators of lung development and injury. We studied NB wild type (WT), lung epithelial cell-targeted VEGF165 doxycycline-inducible overexpressing transgenic (VEGFTG), VEGFTG treated with a NOS1 inhibitor (L-NIO), VEGFTG x NOS2-/- and VEGFTG x NOS3+/- mice in room air (RA) for 7 postnatal (PN) days. Lung morphometry (chord length), vascular markers (Ang1, Ang2, Notch2, vWF, CD31 and VE-cadherin), cell proliferation (Ki67), vascular permeability, injury and oxidative stress markers (hemosiderin, nitrotyrosine and 8-OHdG) were evaluated. VEGF overexpression in RA led to increased chord length and vascular markers at PN7, which were significantly decreased to control values in VEGFTG x NOS2-/- and VEGFTG x NOS3+/- lungs. However, we found no noticeable effect on chord length and vascular markers in the VEGFTG / NOS1 inhibited group. In the NB VEGFTG mouse model, we found VEGF-induced vascular permeability in the NB murine lung was partially dependent on NOS2 and NOS3-signaling pathways. In addition, the inhibition of NOS2 and NOS3 resulted in a significant decrease in VEGF-induced hemosiderin, nitrotyrosine- and 8-OHdG positive cells at PN7. NOS1 inhibition had no significant effect. Our data showed that the complete absence of NOS2 and partial deficiency of NOS3 confers protection against VEGF-induced pathologic lung vascular and alveolar developmental changes, as well as injury markers. Inhibition of NOS1 does not have any modulating role on VEGF-induced changes in the NB lung. Overall, our data suggests that there is a significant differential regulation in the NOS-mediated effects of VEGF overexpression in the developing mouse lung.

Metrics

12 Record Views
18 citations in Web of Science
20 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Industry collaboration
Domestic collaboration
Web of Science research areas
Respiratory System
Logo image