Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat

Author(s)

Schmidt, Augusto F. ^[1] ; Goncalves, Frances L. L. ^[2] ; Regis, Aline C. ^[3] ; Gallindo, Rodrigo M. ^[2] ; Sbragia, Lourenco ^[2]

Affiliation

^[1] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH - USA

^[2] Univ Sao Paulo, Lab Expt Fetal Surg Michael R Harrison, Dept Surg & Anat, Div Pediat Surg, Sch Med Ribeirao Preto, BR-14048900 Ribeirao Preto, SP - Brazil

^[3] Univ Estadual Campinas, Sch Med Sci, Campinas, SP - Brazil

• Document type: Journal article
• Source: American Journal of Obstetrics and Gynecology; v. 207, n. 1 JUL 2012.
• Web of Science Citations: 15

Abstract

OBJECTIVE: We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model. STUDY DESIGN: Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry. Continuous data were analyzed by analysis of variance and Kruskal-Wallis test. RESULTS: CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors, which were reduced in CDH. CONCLUSION: Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH. (AU)

• FAPESP's process: 11/12587-0 - Evaluation in vivo of the effect of corticosteroids and ventilation in oxide nitric pathway on the expression of VEGF and its pulmonary receptors after fetal tracheal occlusion in the congenital diaphragmatic hernia in rats
• Grantee: Frances Lilian Lanhellas Gonçalves
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/00794-1 - Assessment of nitric oxide (NO) in vivo after fetal tracheal occlusion on the expression of VEGF receptors in pulmonary congenital diaphragmatic hernia induced by Nitrofen
• Grantee: Lourenço Sbragia Neto
• Support Opportunities: Regular Research Grants