Published online August 1, 2005
PEDIATRICS
Vol. 116
No. 2
August 2005, pp.
556-557
(doi:10.1542/peds.2005-0698TT)
Vascular Endothelial Growth Factor (VEGF) Induces Remodeling and Enhances Th2-Mediated Sensitization and Inflammation in the Lung
Akaluck Thatayatikom, MD
St Louis, MO
Andrew H. Liu, MD
Denver, CO
Lee CG, Link H, Baluk P, et al. Nat Med. 2004;10:1095–1103
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Purpose of the Study.
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To evaluate the role of vascular endothelial growth factor (VEGF)
in T-helper type 2 (Th2) cell-mediated airway inflammation.
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Study Population.
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Lung-targeted VEGF165 transgenic mice and wild-type mice.
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Methods.
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Phenotypes of transgenic mice with elevated VEGF induced by
doxycycline were studied and compared with wild-type mice. Airway
histologic and physiologic assessments with special stains of
microvasculatures, epithelium cells, inflammatory cells, smooth
muscle cells, and dendritic cells (DCs) as well as allergen
sensitization and methacholine tests were performed.
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Results.
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Both Th2 and epithelial cells were primary sources of VEGF.
Mice with overexpressed VEGF in the airways demonstrated increased
neovascularization, mucous gland metaplasia, edema, collagen
deposition, myocyte hyperplasia with enlarged smooth muscle
bundles, inflammatory cells, activated DCs, airway hyperresponsiveness,
interleukin 13 mRNA expression, Th2 responses, and allergen
sensitization.
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Conclusions.
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VEGF is a potent mediator of allergic airway inflammation by
enhancing allergen sensitization, airway hyperresponsiveness,
Th2 inflammation, and airway remodeling.
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Reviewers’ Comments.
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Well-described airway pathology in asthma includes epithelial
desquamation, goblet cell hyperplasia, collagen deposition below
the basement membrane, smooth muscle hypertrophy/hyperplasia,
and the growth and proliferation of new blood vessels. Although
its pathogenesis is still unclear, VEGF (an inducer of angiogenesis)
recently attracted considerable attention as a major contributor
to airway remodeling. VEGF was first discovered as a vascular
permeability factor >20 years ago. Subsequently, it was revealed
to be a potent inducer of endothelial cell activation and growth.
Overexpression of VEGF and its receptor in the airways has been
demonstrated in stable asthma and during asthma exacerbations
and are reduced by conventional asthma therapies (ie, inhaled
corticosteroids and leukotriene receptor antagonists). The findings
of this study imply an essential role of VEGF in asthma pathogenesis
with links to Th2-mediated airway inflammation and remodeling.
The results of this study may also inform the link of respiratory
syncytial virus infection and asthma development in children,
because respiratory syncytial virus up-regulates VEGF production.
This disclosed role of VEGF highlights a potential therapeutic
role for a VEGF receptor antagonist in asthma.
PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics
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Purpose of the Study.
Study Population.
