Published ahead of print on February 1, 2007, doi:10.1164/rccm.200611-1660PP
Am. J. Respir. Crit. Care Med., Volume 175, Number 10, May 2007, 978-985
A more recent version of this article appeared on May 15, 2007
Submitted on November 19, 2006
Accepted on January 31, 2007
Bronchopulmonary Dysplasia-Where Have all the Vessels Gone?
Bernard Thebaud1* and Steven H Abman2
1 Department of Pediatrics-Division of Neonatology, Vascular Biology Group, University of Alberta, Edmonton, Alberta, Canada,
2 Department of Pediatrics, Pediatric Heart Lung Center, University of Colorado School of Medicine and The Children's Hospital, Denver, Colorado, USA
* To whom correspondence should be addressed. E-mail: bthebaud{at}ualberta.ca.
Bronchopulmonary dysplasia (BPD) 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 suggest 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 BPD.
Key words: Alveoli, Angiogenesis,Oxygen, Stem cells, Lung Development,
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