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  Capillary Changes Precede Disordered Alveolarization in a Mouse Model of Bronchopulmonary Dysplasia

Appuhn V, S., Siebert, S., Myti, D., Wrede, C., Solaligue, D. E. S., Perez-Bravo, D., et al. (2021). Capillary Changes Precede Disordered Alveolarization in a Mouse Model of Bronchopulmonary Dysplasia. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 65(1), 81-91. doi:10.1165/rcmb.2021-0004OC.

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 Creators:
Appuhn V, Svenja, Author
Siebert, Sara, Author
Myti, Despoina1, Author              
Wrede, Christoph, Author
Solaligue, David E. Surate1, Author              
Perez-Bravo, David1, Author              
Brandenberger, Christina, Author
Schipke, Julia, Author
Morty, Rory E.1, Author              
Grothausmann, Roman, Author
Muehlfeld, Christian, Author
Affiliations:
1Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

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Free keywords: ENDOTHELIAL GROWTH-FACTOR; CHRONIC LUNG-DISEASE; PULMONARY-HYPERTENSION; RETINOIC ACID; VEGF; HYPEROXIA; EXPOSURE; ANGIOGENESIS; INJURY; VASCULATUREBiochemistry & Molecular Biology; Cell Biology; Respiratory System; bronchopulmonary dysplasia; lung development; capillary development; stereology; serial block-face scanning electron microscopy;
 Abstract: Bronchopulmonary dysplasia (BPD), the most common sequela of preterm birth, is a severe disorder of the lung that is often associated with long-lasting morbidity. A hallmark of BPD is the disruption of alveolarization, whose pathogenesis is incompletely understood. Here, we tested the vascular hypothesis that disordered vascular development precedes the decreased alveolarization associated with BPD. Neonatal mouse pups were exposed to 7, 14, or 21 days of normoxia (21% O-2) or hyperoxia (85% O-2) with n58-11 for each group. The right lungs were fixed by vascular perfusion and investigated by design-based stereology or three-dimensional reconstruction of data sets obtained by serial block-face scanning EM. The alveolar capillary network of hyperoxia-exposed mice was characterized by rarefaction, partially altered geometry, and widening of capillary segments as shown by three-dimensional reconstruction. Stereology revealed that the development of alveolar epithelium and capillary endothelium was decreased in hyperoxia-exposed mice; however, the time course of these effects was different. That the surface area of the alveolar epithelium was smaller in hyperoxia-exposed mice first became evident at Day 14. In contrast, the surface area of the endothelium was reduced in hyperoxia-exposed mouse pups at Day 7. The thickness of the air-blood barrier decreased during postnatal development in normoxic mice, whereas it increased in hyperoxic mice. The endothelium and the septal connective tissue made appreciable contributions to the thickened septa. In conclusion, the present study provides clear support for the idea that the stunted alveolarization follows the disordered microvascular development, thus supporting the vascular hypothesis of BPD.

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Language(s): eng - English
 Dates: 2021-03-302021-07
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000672720800012
DOI: 10.1165/rcmb.2021-0004OC
PMID: 33784484
 Degree: -

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Title: AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Source Genre: Journal
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Publ. Info: 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA : AMER THORACIC SOC
Pages: - Volume / Issue: 65 (1) Sequence Number: - Start / End Page: 81 - 91 Identifier: ISSN: 1044-1549