help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Galambos, C.
Right arrow Articles by deMello, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Galambos, C.
Right arrow Articles by deMello, D. E.
American Journal of Respiratory Cell and Molecular Biology. Vol. 27, pp. 194-203, 2002
© 2002 American Thoracic Society

Defective Pulmonary Development in the Absence of Heparin-Binding Vascular Endothelial Growth Factor Isoforms

Csaba Galambos, Yin-Shan Ng, Ayoob Ali, Akihiko Noguchi, Stephanie Lovejoy, Patricia A. D'Amore and Daphne E. deMello

Departments of Pathology and Pediatrics, Saint Louis University Health Sciences Center and Cardinal Glennon Children's Hospital, Saint Louis, Missouri; and Schepens Eye Research Institute and Harvard Medical School, Boston, Massachusetts

Address correspondence to: Daphne E. deMello, M.D., Department of Pathology, Cardinal Glennon Children's Hospital, 1465 South Grand Boulevard, Saint Louis, MO 63104. E-mail: demellde{at}slu.edu

Development of the airways, alveoli, and the pulmonary vasculature in the fetus is a process that is precisely controlled. One of the growth factors involved, vascular endothelial growth factor (VEGF), is so critical for embryonic development that in the mouse, elimination of just a single allele is lethal. In the early stages of lung development, the mouse VEGF gene expresses three isoforms (120, 164, and 188) in a distinct temporo-spatial pattern, suggesting a specific function for each. We engineered mice that express only VEGF 120, to study the role of VEGF isoforms in lung development. Lung vessel development in these mice was studied by scanning electron microscopy of Mercox casts of lung vasculature. Airway and air–blood barrier development was analyzed by light microscopy, transmission electron microscopy, immunohistochemistry, and morphometry. In all VEGF120/120 fetuses and pups, lung vascular casts were smaller and less dense compared with 120/+ and wild-type littermates. Although the generation count of pre-acinar vessels was similar in all three genotypes, the most peripheral vessels were dilated and were more widely separated in 120/120 fetuses of all ages, compared with 120/+ and wild-type littermates. In addition, 120/120 animals had fewer air-blood barriers and a decreased airspace-parenchyma ratio compared with 120/+ and wild-type littermates. We concluded that the absence of VEGF 164 and 188 isoforms impairs lung microvascular development and delays airspace maturation, indicating an essential role for heparin-binding VEGF isoforms in normal lung development.

Abbreviations: charge couple device, CCD • diaminobenzidine, DAB • embryonic day 0, E0 • extracellular matrix, ECM • fetal liver kinase receptor, Flk-1 • fms-like tyrosine kinase receptor, Flt-1 • high power fields, hpf • osmium tetroxide, OsO4 • phosphate-buffered saline, PBS • postnatal day 1, PN1 • Type I, T1 • Tris-Na-Blocking buffer, TNB • vascular endothelial growth factor, VEGF




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
S. H. Abman
The Dysmorphic Pulmonary Circulation in Bronchopulmonary Dysplasia: A Growing Story
Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 114 - 115.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. E. De Paepe, C. Patel, A. Tsai, S. Gundavarapu, and Q. Mao
Endoglin (CD105) Up-regulation in Pulmonary Microvasculature of Ventilated Preterm Infants
Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 180 - 187.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
V. Muehlethaler, A. M. Kunig, G. Seedorf, V. Balasubramaniam, and S. H. Abman
Impaired VEGF and nitric oxide signaling after nitrofen exposure in rat fetal lung explants
Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L110 - L120.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
A. C. White, K. J. Lavine, and D. M. Ornitz
FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network
Development, October 15, 2007; 134(20): 3743 - 3752.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
M C Pustovrh, A Jawerbaum, V White, E Capobianco, R Higa, N Martinez, J J Lopez-Costa, and E Gonzalez
The role of nitric oxide on matrix metalloproteinase 2 (MMP2) and MMP9 in placenta and fetus from diabetic rats
Reproduction, October 1, 2007; 134(4): 605 - 613.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
F. A. Groenman, M. Rutter, J. Wang, I. Caniggia, D. Tibboel, and M. Post
Effect of chemical stabilizers of hypoxia-inducible factors on early lung development
Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L557 - L567.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. Thebaud and S. H. Abman
Bronchopulmonary Dysplasia: Where Have All the Vessels Gone? Roles of Angiogenic Growth Factors in Chronic Lung Disease
Am. J. Respir. Crit. Care Med., May 15, 2007; 175(10): 978 - 985.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. Wojciak-Stothard, L. Y. F. Tsang, E. Paleolog, S. M. Hall, and S. G. Haworth
Rac1 and RhoA as regulators of endothelial phenotype and barrier function in hypoxia-induced neonatal pulmonary hypertension
Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1173 - L1182.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. E. De Paepe, Q. Mao, J. Powell, S. E. Rubin, P. DeKoninck, N. Appel, M. Dixon, and F. Gundogan
Growth of Pulmonary Microvasculature in Ventilated Preterm Infants
Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 204 - 211.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. R. Stenmark and V. Balasubramaniam
Angiogenic Therapy for Bronchopulmonary Dysplasia: Rationale and Promise
Circulation, October 18, 2005; 112(16): 2383 - 2385.
[Full Text] [PDF]

Home page
 CirculationHome page
B. Thebaud, F. Ladha, E. D. Michelakis, M. Sawicka, G. Thurston, F. Eaton, K. Hashimoto, G. Harry, A. Haromy, G. Korbutt, et al.
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
Circulation, October 18, 2005; 112(16): 2477 - 2486.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
F. Ladha, S. Bonnet, F. Eaton, K. Hashimoto, G. Korbutt, and B. Thebaud
Sildenafil Improves Alveolar Growth and Pulmonary Hypertension in Hyperoxia-induced Lung Injury
Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 750 - 756.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. R. Grover, T. A. Parker, V. Balasubramaniam, N. E. Markham, and S. H. Abman
Pulmonary hypertension impairs alveolarization and reduces lung growth in the ovine fetus
Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L648 - L654.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. van Tuyl, J. Liu, J. Wang, M. Kuliszewski, D. Tibboel, and M. Post
Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung
Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L167 - L178.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
C. Galambos
Modeling Alveolar Capillary Dysplasia
Circ. Res., September 3, 2004; 95(5): e35 - e35.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. D. Le Cras, R. E. Spitzmiller, K. H. Albertine, J. M. Greenberg, J. A. Whitsett, and A. L. Akeson
VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice
Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L134 - L142.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
K. Ihida-Stansbury, D. M. McKean, S. A. Gebb, J. F. Martin, T. Stevens, R. Nemenoff, A. Akeson, J. Vaughn, and P. L. Jones
Paired-Related Homeobox Gene Prx1 Is Required for Pulmonary Vascular Development
Circ. Res., June 11, 2004; 94(11): 1507 - 1514.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Bornes, M. Boulard, C. Hieblot, C. Zanibellato, J. S. Iacovoni, H. Prats, and C. Touriol
Control of the Vascular Endothelial Growth Factor Internal Ribosome Entry Site (IRES) Activity and Translation Initiation by Alternatively Spliced Coding Sequences
J. Biol. Chem., April 30, 2004; 279(18): 18717 - 18726.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
R. N.N. Han, S. Babaei, M. Robb, T. Lee, R. Ridsdale, C. Ackerley, M. Post, and D. J. Stewart
Defective Lung Vascular Development and Fatal Respiratory Distress in Endothelial NO Synthase-Deficient Mice: A Model of Alveolar Capillary Dysplasia?
Circ. Res., April 30, 2004; 94(8): 1115 - 1123.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Santos, V. I. Peinado, J. Ramirez, J. Morales-Blanhir, R. Bastos, J. Roca, R. Rodriguez-Roisin, and J. A. Barbera
Enhanced Expression of Vascular Endothelial Growth Factor in Pulmonary Arteries of Smokers and Patients with Moderate Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., May 1, 2003; 167(9): 1250 - 1256.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2002 American Thoracic Society.