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PLoS One. 2012;7(12):e51945. doi: 10.1371/journal.pone.0051945. Epub 2012 Dec 20.

Role of EC-SOD overexpression in preserving pulmonary angiogenesis inhibited by oxidative stress.

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  • 1Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of New York and Lilling Family Research laboratory, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA.

Abstract

Angiogenesis is one of the most important processes for normal lung development. Oxidative stress can impair the pulmonary angiogenesis, leading to chronic lung disease or Bronchopulmonary dysplasia (BPD).

OBJECTIVE:

To investigate the protective effects of EC-SOD overexpression on pulmonary angiogenesis on neonates following exposure to acute hyperoxia.

DESIGN/METHODS:

Transgenic (TG) and wild-type (WT) neonatal mice (10 mice per group) were exposed either to air (control group) or 95% O(2) for 7 days starting at birth. After exposure, all animals were sacrificed. ROS concentration was measured in lung homogenates using OxiSelect ROS assay kit. Mean vascular density (MVD) was measured using anti CD34 staining. RNA was extracted and the angiogenesis markers, VEGF, VEGFR1 and VEGFR2 and PECAM-1 were analyzed by RT-q PCR. VGEF protein was measured using Western blots. Endothelial progenitor cells (EPCs) was assayed by flow cytometer.

RESULTS:

There was a significant reduction of ROS in TG hyperoxic neonate group (156±14.2) compared to WT hyperoxic animals (255±35.1). Evaluation of MVD, using anti-CD34, showed marked significant increase of MVD in the TG group following hyperoxic exposure (85±12) in comparison to the WT hyperoxic group (62±8.4), (P<0.05). Among the hyperoxic groups, both RNA and protein of VEGF expression were significantly reduced in the WT animals compared to the TG group (P<0.05). The same trend was found in VEGFR 1 and 2 which were significantly reduced in WT group compared to the TG group (P<0.05). There was no significant difference between hyperoxia TG and control group (P>0.05). PECAM expression was significantly reduced in both hyperoxic compared to normoxic groups (P<0.05). EPC's showed significant reduction in WT hyperoxic group compared to others (P>0.05).

CONCLUSIONS:

EC-SOD plays a key role in preserving angiogenesis by scavenging free radicals which has an inhibitory effect on angiogenesis process in neonatal mice lung following exposure to hyperoxia.

PMID:
23284826
[PubMed - indexed for MEDLINE]
PMCID:
PMC3527376
Free PMC Article
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