Antioxidant defenses in the preterm lung: role for hypoxia-inducible factors in BPD?
Pulmonary antioxidants and their therapeutic implications have been extensively studied during past decades. The purpose of this review is to briefly summarize the key findings of these studies as well as to elaborate on some novel approaches with respect to potential preventive treatments for neonatal chronic lung disease bronchopulmonary dysplasia (BPD). Such new ideas include, for example, modification of transcription factors governing the hypoxic response pathways, important in angiogenesis, cell survival, and glycolytic responses. The fundamental strategy behind that approach is that fetal lung normally develops under hypoxic conditions and that this hypoxic, growth-favoring environment is interrupted by a premature birth. Importantly, during fetal lung development, alveolar development appears to be dependent on vascular development. Therefore, enhancement of signaling factors that occur during hypoxic fetal life ('continued fetal life ex utero'), including angiogenic responses, could potentially lead to improved lung growth and thereby alleviate the alveolar and vascular hypoplasia characteristic of BPD.
Asikainen
Tiina M
TM
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA. asikainent@njc.org
White
Carl W
CW
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D047928:Premature Birth / Q000209:etiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D000099162:Endothelial PAS Domain-Containing Protein 1
D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015534:Trans-Activators; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human