Chronic intermittent hypoxia induces lung growth in adult mice
| Autor: | Allen C. Myers, Vsevolod Y. Polotsky, Shannon Bevans-Fonti, Dmitry N. Grigoryev, Luciano F. Drager, Christian Reinke, Alan R. Schwartz, Wayne Mitzner, Robert A. Wise |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Platelet-derived growth factor Physiology medicine.medical_treatment Biology Andrology Mice chemistry.chemical_compound Transforming Growth Factor beta Physiology (medical) medicine Animals Lung volumes Respiratory system Hypoxia Lung DNA Primers Oligonucleotide Array Sequence Analysis Platelet-Derived Growth Factor Sleep Apnea Obstructive Base Sequence Gene Expression Profiling Growth factor Intermittent hypoxia Articles Cell Biology Mice Inbred C57BL Disease Models Animal Vascular endothelial growth factor A Receptors Vascular Endothelial Growth Factor medicine.anatomical_structure chemistry Terminal deoxynucleotidyl transferase Chronic Disease |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 300:L266-L273 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00239.2010 |
| Popis: | Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality, which have been attributed to intermittent hypoxia (IH). The effects of IH on lung structure and function are unknown. We used a mouse model of chronic IH, which mimics the O2profile in patients with OSA. We exposed adult C57BL/6J mice to 3 mo of IH with a fraction of inspired oxygen (FiO2) nadir of 5% 60 times/h during the 12-h light phase. Control mice were exposed to room air. Lung volumes were measured by quasistatic pressure-volume (PV) curves under anesthesia and by water displacement postmortem. Lungs were processed for morphometry, and the mean airspace chord length (Lm) and alveolar surface area were determined. Lung tissue was stained for markers of proliferation (proliferating cell nuclear antigen), apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling), and type II alveolar epithelial cells (surfactant protein C). Gene microarrays were performed, and results were validated by real-time PCR. IH increased lung volumes by both PV curves (air vs. IH, 1.16 vs. 1.44 ml, P < 0.0001) and water displacement ( P < 0.01) without changes in Lm, suggesting that IH increased the alveolar surface area. IH induced a 60% increase in cellular proliferation, but the number of proliferating type II alveolocytes tripled. There was no increase in apoptosis. IH upregulated pathways of cellular movement and cellular growth and development, including key developmental genes vascular endothelial growth factor A and platelet-derived growth factor B. We conclude that IH increases alveolar surface area by stimulating lung growth in adult mice. |
| Databáze: | OpenAIRE |
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