Your browser doesn't support javascript.
loading
Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice.
Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert; Navarro, Edwin; Jain, Noopur; Carandang, Francis; Peterson, Joanna; Mokres, Lucia; Milla, Carlos; Preuss, Stefanie; Alcazar, Miguel Alejandre; Khan, Suleman; Masumi, Juliet; Ferreira-Tojais, Nancy; Mujahid, Sana; Starcher, Barry; Rabinovitch, Marlene; Bland, Richard.
Afiliación
  • Hilgendorff A; Department of Pediatrics, Stanford University, Stanford, California; Comprehensive Pneumology Center, Ludwig-Maximilian University, Munich, Germany; and.
  • Parai K; Department of Pediatrics, Stanford University, Stanford, California;
  • Ertsey R; Department of Pediatrics, Stanford University, Stanford, California;
  • Navarro E; Department of Pediatrics, Stanford University, Stanford, California;
  • Jain N; Department of Pediatrics, Stanford University, Stanford, California;
  • Carandang F; Department of Pediatrics, Stanford University, Stanford, California;
  • Peterson J; Department of Pediatrics, Stanford University, Stanford, California;
  • Mokres L; Department of Pediatrics, Stanford University, Stanford, California;
  • Milla C; Department of Pediatrics, Stanford University, Stanford, California;
  • Preuss S; Department of Pediatrics, Stanford University, Stanford, California;
  • Alcazar MA; Department of Pediatrics, Stanford University, Stanford, California;
  • Khan S; Department of Pediatrics, Stanford University, Stanford, California;
  • Masumi J; Department of Pediatrics, Stanford University, Stanford, California;
  • Ferreira-Tojais N; Department of Pediatrics, Stanford University, Stanford, California;
  • Mujahid S; Department of Pediatrics, Stanford University, Stanford, California;
  • Starcher B; Department of Biochemistry, University of Texas, Tyler, Texas.
  • Rabinovitch M; Department of Pediatrics, Stanford University, Stanford, California;
  • Bland R; Department of Pediatrics, Stanford University, Stanford, California; rbland@stanford.edu.
Am J Physiol Lung Cell Mol Physiol ; 308(5): L464-78, 2015 Mar 01.
Article en En | MEDLINE | ID: mdl-25539853
Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice (Eln(+/-)) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type (Eln(+/+)) and Eln(+/-) littermates at baseline and after MV with air for 8-24 h. Lungs of unventilated Eln(+/-) mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with 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 with Eln(+/+) mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency 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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Respiración Artificial / Elastina / Matriz Extracelular / Haploinsuficiencia / Remodelación Vascular / Pulmón Límite: Animals Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Respiración Artificial / Elastina / Matriz Extracelular / Haploinsuficiencia / Remodelación Vascular / Pulmón Límite: Animals Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos