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Neonatal mice (1-day-old) were exposed to 80% O<jats:sub>2<\/jats:sub>at Denver's altitude (= 65% at sea level) or room air for 10 days. Adult mice were also exposed for comparison. Blood, lung, and bone marrow were harvested after hyperoxia. Hyperoxia decreased pulmonary vascular density by 72% in neonatal but not adult mice. In contrast to the adult, hyperoxia simplified distal lung structure neonatal mice. Moderate hyperoxia reduced EPCs (CD45\u2212\/Sca-1+\/CD133+\/VEGFR-2+) in the blood (55%; P &lt; 0.03), bone marrow (48%; P &lt; 0.01), and lungs (66%; P &lt; 0.01) of neonatal mice. EPCs increased in bone marrow (2.5-fold; P &lt; 0.01) and lungs (2-fold; P &lt; 0.03) of hyperoxia-exposed adult mice. VEGF, nitric oxide (NO), and erythropoietin (Epo) contribute to mobilization and homing of EPCs. Lung VEGF, VEGF receptor-2, endothelial NO synthase, and Epo receptor expression were reduced by hyperoxia in neonatal but not adult mice. We conclude that moderate hyperoxia decreases vessel density, impairs lung structure, and reduces EPCs in the circulation, bone marrow, and lung of neonatal mice but increases EPCs in adults. This developmental difference may contribute to the increased susceptibility of the developing lung to hyperoxia and may contribute to impaired lung vascular and alveolar growth in BPD.<\/jats:p>","DOI":"10.1152\/ajplung.00347.2006","type":"journal-article","created":{"date-parts":[[2007,1,6]],"date-time":"2007-01-06T01:48:08Z","timestamp":1168048088000},"page":"L1073-L1084","source":"Crossref","is-referenced-by-count":201,"title":["Hyperoxia reduces bone marrow, circulating, and lung endothelial progenitor cells in the developing lung: implications for the pathogenesis of bronchopulmonary dysplasia"],"prefix":"10.1152","volume":"292","author":[{"given":"Vivek","family":"Balasubramaniam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cela F.","family":"Mervis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Maxey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil E.","family":"Markham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Abman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200307-908OC"},{"key":"R2","unstructured":"Abman S.Pulmonary hypertension in chronic lung disease of infancy: pathogenesis, pathophysiology, and treatment. 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