help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on February 18, 2005, doi:10.1165/rcmb.2004-0287OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2004-0287OCv1
32/5/420    most recent
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 McGrath-Morrow, S. A.
Right arrow Articles by Tuder, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McGrath-Morrow, S. A.
Right arrow Articles by Tuder, R. M.
American Journal of Respiratory Cell and Molecular Biology. Vol. 32, pp. 420-427, 2005
© 2005 American Thoracic Society
DOI: 10.1165/rcmb.2004-0287OC

Vascular Endothelial Growth Factor Receptor 2 Blockade Disrupts Postnatal Lung Development

Sharon A. McGrath-Morrow, Cecilia Cho, Chung Cho, Lijie Zhen, Daniel J. Hicklin and Rubin M. Tuder

Department of Pediatrics, Eudowood Division of Pediatric Respiratory Sciences; Division of Cardiopulmonary Pathology, Department of Pathology; and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland; and Imclone Systems Inc., New York, New York

Correspondence and requests for reprints should be addressed to Dr. Sharon McGrath-Morrow, Department of Pediatric Pulmonary, Johns Hopkins Hospital, Park 316 N. Wolfe St., Baltimore, MD 21287-2533. E-mail address: smorrow{at}jhmi.edu

Vascular endothelial growth factor (VEGF) is necessary for normal postnatal lung development and may underlie the structural lung damage that follows hyperoxic exposure. To determine the individual roles of VEGF receptors (VEGFR) 2 and 1 on postnatal lung growth, neonatal mice were treated with neutralizing antibodies to VEGFR-2 (DC101) or VEGFR-1 (MF1) in the perinatal period. At 1 wk of age, mice treated with DC101 on Days 2 and 4 of life had significantly larger mean alveolar diameters consistent with impaired alveolization. By 2 wk of age, however, perinatally treated DC101 mice had normal-appearing alveolar structure. Mice exposed to perinatal hyperoxia (O2) also had larger mean alveolar diameters at 1 wk of age, but unlike DC101-treated mice, their mitotic index was decreased at 1 wk of age and they had persistent alveolar enlargement beyond the first 2 wk of life. The O2-treated lung also had an increase in caspase 3 at 1 wk of age and significantly greater expression of nitrotyrosine at 2 wk of age. Therefore, VEGFR-2 blockade in the perinatal period disrupts early alveolar development, but the effect is reversible with time, whereas hyperoxic lung injury is associated with ongoing lung structural impairment.

Key Words: VEGF receptor 2 • postnatal lung growth • hyperoxia




This article has been cited by other articles:


Home page
 Physiol. GenomicsHome page
O. Boucherat, M.-L. Franco-Montoya, C. Thibault, R. Incitti, B. Chailley-Heu, C. Delacourt, and J. R. Bourbon
Gene expression profiling in lung fibroblasts reveals new players in alveolarization
Physiol Genomics, December 19, 2007; 32(1): 128 - 141.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. D. Bland, L. M. Mokres, R. Ertsey, B. E. Jacobson, S. Jiang, M. Rabinovitch, L. Xu, E. S. Shinwell, F. Zhang, and M. A. Beasley
Mechanical ventilation with 40% oxygen reduces pulmonary expression of genes that regulate lung development and impairs alveolar septation in newborn mice
Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1099 - L1110.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J.-R. Tang, G. Seedorf, V. Balasubramaniam, A. Maxey, N. Markham, and S. H. Abman
Early inhaled nitric oxide treatment decreases apoptosis of endothelial cells in neonatal rat lungs after vascular endothelial growth factor inhibition
Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1271 - L1280.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. D. Bland, L. Xu, R. Ertsey, M. Rabinovitch, K. H. Albertine, K. A. Wynn, V. H. Kumar, R. M. Ryan, D. D. Swartz, K. Csiszar, et al.
Dysregulation of pulmonary elastin synthesis and assembly in preterm lambs with chronic lung disease
Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1370 - L1384.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Yee, P. F. Vitiello, J. M. Roper, R. J. Staversky, T. W. Wright, S. A. McGrath-Morrow, W. M. Maniscalco, J. N. Finkelstein, and M. A. O'Reilly
Type II epithelial cells are critical target for hyperoxia-mediated impairment of postnatal lung development
Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1101 - L1111.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
R. M. Tuder, T. Yoshida, W. Arap, R. Pasqualini, and I. Petrache
State of the Art. Cellular and Molecular Mechanisms of Alveolar Destruction in Emphysema: An Evolutionary Perspective
Proceedings of the ATS, August 1, 2006; 3(6): 503 - 510.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
S. D. Shapiro
Extracellular matrix in lung disease. Proceedings of the Twenty-First Transatlantic Airway Conference.
Proceedings of the ATS, July 1, 2006; 3(5): 397 - 455.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
I. Petrache, I. Fijalkowska, L. Zhen, T. R. Medler, E. Brown, P. Cruz, K.-H. Choe, L. Taraseviciene-Stewart, R. Scerbavicius, L. Shapiro, et al.
A Novel Antiapoptotic Role for {alpha}1-Antitrypsin in the Prevention of Pulmonary Emphysema
Am. J. Respir. Crit. Care Med., June 1, 2006; 173(11): 1222 - 1228.
[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 HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society.