426 - Maternal Vitamin D Deficiency Alters Pulmonary Endothelial Cell Growth and mRNA Expression in Newborn Rats

Poster Number: 426
Publication Number: 426.429

Tania Gonzalez, University of Colorado School of Medicine, Aurora, CO, United States; Elisa Bye, University of Colorado School of Medicine, Aurora, CO, United States; Nicholas W. Galambos, University of Colorado School of Medicine, Boulder, CO, United States; Gregory J. Seedorf, University of Colorado School of Medicine, Aurora, CO, United States; James Fleet, University of Texas at Austin, Austin, TX, United States; Steven Abman, University of Colorado School of Medicine, denver, CO, United States; Erica Mandell, University of Colorado School of Medicine, Aurora, CO, United States

Background: Vitamin D deficiency (VDD) during pregnancy is associated with abnormal lung development, though mechanisms are understudied. We have shown that 1,25(OH)2 vitamin D (VD) preserves lung structure and prevents pulmonary hypertension (PH) in an experimental model of bronchopulmonary dysplasia, and that 1,25(OH)2 VD treatment increases pulmonary artery endothelial cell growth and function. However, the direct effects of maternal VDD on pulmonary endothelial cell (PEC) growth and function are unknown.

Objective: We seek to determine whether maternal VDD alters growth and mRNA expression of PEC from newborn rats at birth and whether these changes persist during infancy.

Design/Methods: Female rats were fed VDD chow and shielded from UV-B light to achieve 25(OH) VD levels less than 10 ng/ml before mating. PEC were isolated from offspring of VDD (VDD) or control (CTL) dams at postnatal days 0 and 14. PECs were used for proliferation assays and response to exogenous VEGF, 1,25(OH)2 VD, and 25(OH) VD. PEC lysates were also collected for RT-qPCR analysis.

Results: At both D0 and D14, PEC isolated from VDD pups demonstrate decreased growth compared to CTL (p < 0.01). VEGF, 1,25(OH)2 VD, and 25(OH) VD treatments increased baseline CTL PEC growth from both D0 and D14 pups (p < 0.01). In contrast, these treatments did not increase D0 VDD PEC growth. At D14, VDD PEC were not responsive to the vitamin D metabolites. However, VEGF treatment increased growth of D14 VDD PEC compared to untreated D14 VDD PEC (p < 0.01), but this growth response was blunted compared to the impact of VEGF on D14 CTL PEC. At D0, VDD PEC had reduced expression of KDR and eNOS mRNA and had increased VEGF expression compared to D0 CTL PEC (p < 0.01). At D14, VDD PEC had elevated VDR mRNA expression compared to CTL D14 PEC (p < 0.01).
 Conclusion(s): We found that D0 PEC from newborn offspring of maternal VDD dams demonstrate decreased baseline PEC growth and were not responsive to angiogenic stimuli. At D14, VDD PEC grew poorly at baseline and had increased responsiveness to VEGF but not 1,25(OH)2 VD or 25(OH) VD treatment. We speculate that maternal VDD disrupts normal PEC function, which persists into postnatal life and may contribute to high risk for late cardiopulmonary disease.