Altered Prostanoid Metabolism Contributes to Impaired Angiogenesis in Persistent Pulmonary Hypertension of the Newborn

Background—PPHN is associated with decreased lung angiogenesis and impaired pulmonary vasodilatation at birth. Prostanoids are important modulators of vascular tone and angiogenesis. We hypothesized that altered levels of prostacyclin (PGI2), a potent vasodilator, and thromboxane (TXA2), a vasoconstrictor, contribute to impaired angiogenesis of pulmonary artery endothelial cells (PAEC) in PPHN. Methods—PAEC were isolated from fetal lambs with PPHN induced by prenatal ductus arteriosus constriction or sham operated controls. Expression and activity of PGI2 synthase (PGIS) and TXA2 synthase (TXAS), expression of cyclooxygenases 1 and 2 (COX-1 and COX-2) and the role of PGIS/TXAS alterations in angiogenesis were investigated in PAEC from PPHN and control lambs. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Address correspondence and reprint requests to: Girija G. Konduri, M.D., Ste. C410, 999N 92nd Street, Wauwatosa, WI 53226, Tel: 414-266-6820, Fax: 414-266-6979, [email protected]. *Co-senior authors DISCLOSURE STATEMENT: Authors do not have any financial ties to products in the study or potential/perceived conflicts of interest. HHS Public Access Author manuscript Pediatr Res. Author manuscript; available in PMC 2015 September 12. Published in final edited form as: Pediatr Res. 2015 March ; 77(3): 455–462. doi:10.1038/pr.2014.209. A uhor M anscript