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Hilgendorff, A. ; Parai, K.* ; Ertsey, R.* ; Navarro, E.F.* ; Jain, N.* ; Carandang, F.* ; Peterson, J.* ; Mokres, L.M.* ; Milla, C.* ; Preuss, S.* ; Alejandre Alcazar, M.A.* ; Khan, S.* ; Masumi, J.* ; Ferreira-Tojais, N.* ; Mujahid, S.* ; Starcher, B.C.* ; Rabinovitch, M.* ; Bland, R.D.*

Lung matrix and vascular remodeling in mechanically ventilated elastin haplo-insufficient (Eln+/-) newborn mice.

Am. J. Physiol. Lung Cell Mol. Physiol. 308, L464-L478 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Elastin plays a pivotal role in lung development. We therefore queried if elastin haplo-insufficient newborn mice (Eln(+/-)) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. As mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haplo-insufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5d-old wild-type (Eln(+/+)) and Eln(+/-) littermates at baseline, and after MV with air for 8-24h. Lungs of unventilated Eln(+/-) mice contained ~50% less elastin and ~100% more collagen-1 and lysyl oxidase compared to Eln(+/+) pups. Eln(+/-) lungs contained fewer capillaries than Eln(+/+) lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln(+/+) neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln(+/-) mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln(+/-) than in Eln(+/+) pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln(+/-) compared to Eln(+/+) mice, was similar in both groups after MV. These results suggest that elastin haplo-insufficiency adversely impacts pulmonary angiogenesis, and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln(+/+) and Eln(+/-) mice. Paucity of lung capillaries in Eln(+/-) newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln(+/-) mice.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Elastic Fiber Formation ; Extracellular Matrix Components - Elastin, Collagen, Lysyl Oxidase And Fibrillins ; Lung Cell Apoptosis ; Lung Growth And Development ; Pulmonary Capillaries; Preterm Lambs; Extracellular-matrix; Alveolar Septation; Rat Lung; Injury; Angiogenesis; Apoptosis; Growth; Disease; Morphogenesis
ISSN (print) / ISBN 1040-0605
e-ISSN 1522-1504
Journal American Journal of Physiology - Lung Cellular and Molecular Physiology
Quellenangaben Volume: 308, Issue: 5, Pages: L464-L478 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place Bethesda, Md. [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)