Lung hypoplasia contributes to the pathogenesis of several cardiorespiratory diseases in children, including idiopathic lung hypoplasia, congenital diaphragmatic hemia, and bronchopulmonary dysplasia. Each of these disorders is associated with abnormal alveolar development and a high risk for pulmonary hypertension (PH). The Fawn Hooded Rat (FHR), a genetic strain characterized by platelet abnormalities and systemic hypertension, develops pulmonary hypertension (PH) when exposed to mild decreases in alveolar PO2 (Denver's altitude). In previous studies we have observed at normal lung development and hypoplasia (alveolar simplification) in the FHR at Denver's altitude. Various growth factors and their receptors have been described as having important roles in lung development, including vascular endothelial growth factor (VEGF). VEGF is an endothelial cell mitogen produced in the early fetal lung and plays a role in regulating vasculogenesis and angiogenesis during development. In addition, lung VEGF content is increased in rat models of chronic hypoxia induced PH To determine if VEGF gene expression is abnormal in the FHR and therefore might contribute to lung hypoplasia and PH, we measured lung VEGF mRNA levels by Northern blot analysis. Lung RNA was isolated from late gestation fetal, 1 day, 7 day and 10 week FHRs and age matched controls (Sprague Dawley, SDR). Lung VEGF mRNA levels were decreased in fetal FHRs compared to controls (p< .001). There were no significant differences between the groups at 1 day and 7 days of age. In contrast, lung VEGF mRNA levels were elevated in 10 week FHRs compared to SDRs (p< .05). In situ hybridization of VEGF mRNA was performed on formalin fixed lung (issue at each age. VEGF mRNA was predominantly expressed in type II alveolar epithelial cells. In summary, lung VEGF mRNA expression is reduced in the FHR fetus. As observed in rats with chronic hypoxic PH, VEGF mRNA is increased in adult FHR lungs. We speculate that reduced VEGF gene expression may play a role in the lung hypoplasia and the development of PH in the FHR at Denver's altitude.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)