title: Vasculoprotective effects of heme oxygenase-1 in a murine model of hyperoxia-induced bronchopulmonary dysplasia.
abstract: Bronchopulmonary dysplasia (BPD) is characterized by simplified alveolarization and arrested vascular development of the lung with associated evidence of endothelial dysfunction, inflammation, increased oxidative damage, and iron deposition. Heme oxygenase-1 (HO-1) has been reported to be protective in the pathogenesis of diseases of inflammatory and oxidative etiology. Because HO-1 is involved in the response to oxidative stress produced by hyperoxia and is critical for cellular heme and iron homeostasis, it could play a protective role in BPD. Therefore, we investigated the effect of HO-1 in hyperoxia-induced lung injury using a neonatal transgenic mouse model with constitutive lung-specific HO-1 overexpression. Hyperoxia triggered an increase in pulmonary inflammation, arterial remodeling, and right ventricular hypertrophy that was attenuated by HO-1 overexpression. In addition, hyperoxia led to pulmonary edema, hemosiderosis, and a decrease in blood vessel number, all of which were markedly improved in HO-1 overexpressing mice. The protective vascular response may be mediated at least in part by carbon monoxide, due to its anti-inflammatory, antiproliferative, and antiapoptotic properties. HO-1 overexpression, however, did not prevent alveolar simplification nor altered the levels of ferritin and lactoferrin, proteins involved in iron binding and transport. Thus the protective mechanisms elicited by HO-1 overexpression primarily preserve vascular growth and barrier function through iron-independent, antioxidant, and anti-inflammatory pathways.
authors.affiliation: Harvard Division of Newborn Medicine, Children’s Hospital Boston, MA 02115, USA.
authors.forename: Angeles
authors.initials: A
authors.lastname: Fernandez-Gonzalez
authors.forename: S
authors.initials: S
authors.lastname: Alex Mitsialis
authors.forename: Xianlan
authors.initials: X
authors.lastname: Liu
authors.forename: Stella
authors.initials: S
authors.lastname: Kourembanas
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000201:enzymology*; D004195:Disease Models, Animal; D005293:Ferritins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006486:Hemosiderosis / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D010100:Oxygen / Q000008:administration & dosage* / Q000009:adverse effects; D011654:Pulmonary Edema / Q000201:enzymology
chemical_list: D005293:Ferritins; D007501:Iron; D051547:Heme Oxygenase-1; D007781:Lactoferrin; D010100:Oxygen