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

PloS One
Mansoor A SyedVineet Bhandari

Abstract

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 pathwa...Continue Reading

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Citations

Nov 9, 2017·Molecular and Cellular Pediatrics·Prajakta Oak, Anne Hilgendorff
Jun 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Saleh A AlmatroodiArshad Husain Rahmani
Jan 4, 2021·The Journal of Nutritional Biochemistry·Shaniya AhmadMansoor Ali Syed
Feb 6, 2020·European Journal of Pharmacology·Hai Lin, Xinbao Wang

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Methods Mentioned

BETA
bronchoalveolar lavage
transgenic
PCR
ELISA

Software Mentioned

Image J
GraphPad Prism
NIH image J

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