RGD Reference Report - Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. - Rat Genome Database

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Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization.

Authors: Thebaud, B  Ladha, F  Michelakis, ED  Sawicka, M  Thurston, G  Eaton, F  Hashimoto, K  Harry, G  Haromy, A  Korbutt, G  Archer, SL 
Citation: Thebaud B, etal., Circulation. 2005 Oct 18;112(16):2477-86.
RGD ID: 1580552
Pubmed: PMID:16230500   (View Abstract at PubMed)
DOI: DOI:10.1161/CIRCULATIONAHA.105.541524   (Journal Full-text)

BACKGROUND: Bronchopulmonary dysplasia (BPD) and pulmonary emphysema, both significant global health problems, are characterized by a loss of alveoli. Vascular endothelial growth factor (VEGF) is a trophic factor required for endothelial cell survival and is abundantly expressed in the lung. METHODS AND RESULTS: We report that VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries, mimicking BPD. In hyperoxia-induced BPD in newborn rats, air space enlargement and loss of lung capillaries are associated with decreased lung VEGF and VEGFR-2 expression. Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development in this model of irreversible lung injury. Combined VEGF and angiopoietin-1 gene transfer matures the new vasculature, reducing the vascular leakage seen in VEGF-induced capillaries. CONCLUSIONS: These findings underscore the importance of the vasculature in what is traditionally thought of as an airway disease and open new therapeutic avenues for lung diseases characterized by irreversible loss of alveoli through the modulation of angiogenic growth factors.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
angiogenesis  IMP 1580552 RGD 
lung alveolus development  IMP 1580552 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vegfa  (vascular endothelial growth factor A)


Additional Information