Abstract 2091 Pulmonary: General Lung Biology Poster Symposium, Sunday, 5/2

Lung hypoplasia contributes to the pathogenesis of several cardiorespiratory diseases in children and is associated with abnormal alveolar development and a high risk for pulmonary hypertension (PH). The Fawn Hooded Rat (FHR) develops accelerated PH with mild decreases in alveolar PO2 (Denver's altitude). In previous studies, we have observed lung hypoplasia (decreased alveolization) in the FHR at Denver's altitude. Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a role in regulating vasculogenesis and angiogenesis in normal lung development and is increased in rat models of chronic hypoxia-induced PH.

Whether altered VEGF expression contributes to abnormal lung development in the FHR is unknown. To determine if VEGF gene expression is abnormal in FHR, we measured lung VEGF gene expression at various ages in FHR and a normal rat strain (Sprague Dawley, SDR). Lung VEGF mRNA levels were decreased in fetal FHR compared to SDR (P<0.001). There were no differences between FHR and SDR at 1 and 7 days of age, while lung VEGF mRNA levels were elevated in adult (10 week old) FHR compared to SDR (p<0.05). In situ hybridization showed that VEGF mRNA was predominantly expressed in type II alveolar epithelial cells. Since hyperbaria (to achieve sea level PO2) reduces the development of PH in the FHR at Denver's altitude, we examined the effect of perinatal hyperbaric exposure on VEGF mRNA expression in FHR. After 3 weeks of either prenatal or pre-and-postnatal hyperbaria VEGF mRNA levels were reduced compared to FHR raised at Denver's altitude. In summary, lung VEGF mRNA expression is reduced in the FHR fetus, increased with progressive PH in the adult FHR, and decreased by postnatal hyperbaria. We speculate that altered VEGF gene expression may play a role in disrupted lung development and the high risk for PH in the FHR. (Figure)

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