Published ahead of print on February 1, 2007, doi:10.1164/rccm.200611-1660PP
American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 978-985, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200611-1660PP
Bronchopulmonary DysplasiaWhere Have All the Vessels Gone? Roles of Angiogenic Growth Factors in Chronic Lung Disease
Bernard Thébaud1 and
Steven H. Abman2
1 Department of Pediatrics, Division of Neonatology, Vascular Biology Group, University of Alberta, Edmonton, Alberta, Canada; and 2 Department of Pediatrics, Pediatric Heart Lung Center, University of Colorado School of Medicine and the Children's Hospital, Denver, Colorado
Correspondence and requests for reprints should be addressed to Bernard Thébaud, Department of Pediatrics, Division of Neonatology, Vascular Biology Group, University of Alberta, HMRC 407, Edmonton, AB, T6G 2S2, Canada. E-mail: bthebaud{at}ualberta.ca
ABSTRACT
Bronchopulmonary dysplasia and emphysema are significant global health problems at the extreme stages of life. Both are characterized by arrested alveolar development or loss of alveoli, respectively. Both lack effective treatment strategies. Knowledge about the genetic control of branching morphogenesis in mammals derives from investigations of the respiratory system in Drosophila, but mechanisms that regulate alveolar development remain poorly understood. Even less is known about regulation of the growth and development of the pulmonary vasculature. Understanding how alveoli and the underlying capillary network develop, and how these mechanisms are disrupted in disease states, are critical for developing effective therapies for lung diseases characterized by impaired alveolar structure. Recent observations have challenged old notions that the development of the blood vessels in the lung passively follows that of the airways. Rather, increasing evidence suggests that lung blood vessels actively promote alveolar growth during development and contribute to the maintenance of alveolar structures throughout postnatal life. Our working hypothesis is that disruption of angiogenesis impairs alveolarization, and that preservation of vascular growth and endothelial survival promotes growth and sustains the architecture of the distal airspace. Furthermore, the explosion of interest in stem cell biology suggests potential roles for endothelial progenitor cells in the pathogenesis or treatment of lung vascular disease. In this Pulmonary Perspective, we review recent data on the importance of the lung circulation, specifically examining the relationship between dysmorphic vascular growth and impaired alveolarization, and speculate on how these new insights may lead to novel therapeutic strategies for bronchopulmonary dysplasia.
Key Words: lung injury oxygen angiogenesis newborn nitric oxide
This article has been cited by other articles:

|
 |

|
 |
 
A. Borghesi, M. Massa, R. Campanelli, L. Bollani, C. Tzialla, T. A. Figar, G. Ferrari, E. Bonetti, G. Chiesa, A. de Silvestri, et al.
Circulating Endothelial Progenitor Cells in Preterm Infants with Bronchopulmonary Dysplasia
Am. J. Respir. Crit. Care Med.,
September 15, 2009;
180(6):
540 - 546.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Bose, L. J. Van Marter, M. Laughon, T. M. O'Shea, E. N. Allred, P. Karna, R. A. Ehrenkranz, K. Boggess, A. Leviton, and for the Extremely Low Gestational Age Newborn Stud
Fetal Growth Restriction and Chronic Lung Disease Among Infants Born Before the 28th Week of Gestation
Pediatrics,
September 1, 2009;
124(3):
e450 - e458.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Lukkarinen, A. Hogmalm, U. Lappalainen, and K. Bry
Matrix Metalloproteinase-9 Deficiency Worsens Lung Injury in a Model of Bronchopulmonary Dysplasia
Am. J. Respir. Cell Mol. Biol.,
July 1, 2009;
41(1):
59 - 68.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B A Darlow, C Gilbert, G E Quinn, R Azad, A L Ells, A Fielder, and A Zin
Promise and potential pitfalls of anti-VEGF drugs in retinopathy of prematurity
Br J Ophthalmol,
July 1, 2009;
93(7):
986 - 986.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R.-J. Teng, A. Eis, I. Bakhutashvili, N. Arul, and G. G. Konduri
Increased superoxide production contributes to the impaired angiogenesis of fetal pulmonary arteries with in utero pulmonary hypertension
Am J Physiol Lung Cell Mol Physiol,
July 1, 2009;
297(1):
L184 - L195.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Ahmad, S. Ahmad, L. Glover, S. M. Miller, J. M. Shannon, X. Guo, W. A. Franklin, J. P. Bridges, J. B. Schaack, S. P. Colgan, et al.
Adenosine A2A receptor is a unique angiogenic target of HIF-2{alpha} in pulmonary endothelial cells
PNAS,
June 30, 2009;
106(26):
10684 - 10689.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bhandari and V. Bhandari
Pitfalls, Problems, and Progress in Bronchopulmonary Dysplasia
Pediatrics,
June 1, 2009;
123(6):
1562 - 1573.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Woyda, S. Koebrich, I. Reiss, S. Rudloff, S. S. Pullamsetti, A. Ruhlmann, N. Weissmann, H. A. Ghofrani, A. Gunther, W. Seeger, et al.
Inhibition of phosphodiesterase 4 enhances lung alveolarisation in neonatal mice exposed to hyperoxia
Eur. Respir. J.,
April 1, 2009;
33(4):
861 - 870.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Parmar, L. R. Berry, M. Post, and A. K. C. Chan
Effect of covalent antithrombin-heparin complex on developmental mechanisms in the lung
Am J Physiol Lung Cell Mol Physiol,
March 1, 2009;
296(3):
L394 - L403.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Gien, G. J. Seedorf, V. Balasubramaniam, N. Tseng, N. Markham, and S. H. Abman
Chronic intrauterine pulmonary hypertension increases endothelial cell Rho kinase activity and impairs angiogenesis in vitro
Am J Physiol Lung Cell Mol Physiol,
October 1, 2008;
295(4):
L680 - L687.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. M. Wong, A. N. Lees, J. Louw, F. Y. Lee, N. French, K. Gain, C. P. Murray, A. Wilson, and D. C. Chambers
Emphysema in young adult survivors of moderate-to-severe bronchopulmonary dysplasia
Eur. Respir. J.,
August 1, 2008;
32(2):
321 - 328.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
M. E. De Paepe, S. Gundavarapu, U. Tantravahi, J. R. Pepperell, S. A. Haley, F. I. Luks, and Q. Mao
Fas-Ligand-Induced Apoptosis of Respiratory Epithelial Cells Causes Disruption of Postcanalicular Alveolar Development
Am. J. Pathol.,
July 1, 2008;
173(1):
42 - 56.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. S. Prince
Hyperoxia and EGFL7: saving cells from too much of a good thing
Am J Physiol Lung Cell Mol Physiol,
January 1, 2008;
294(1):
L15 - L16.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
B. Thebaud and S. Abman
Depletion of Endothelial Progenitor Cells May Link Pulmonary Fibrosis and Pulmonary Hypertension
Am. J. Respir. Crit. Care Med.,
October 1, 2007;
176(7):
725 - 725.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. P. Fadini, M. Schiavon, F. Rea, A. Avogaro, and C. Agostini
Depletion of Endothelial Progenitor Cells May Link Pulmonary Fibrosis and Pulmonary Hypertension
Am. J. Respir. Crit. Care Med.,
October 1, 2007;
176(7):
724 - 725.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. M. Asikainen and C. W. White
HIF stabilizing agents: shotgun or scalpel?
Am J Physiol Lung Cell Mol Physiol,
September 1, 2007;
293(3):
L555 - L556.
[Full Text]
[PDF]
|
 |
|
Copyright © 2007 American Thoracic Society
|
|
|