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Metabolism of PGE2 by prostaglandin dehydrogenase is essential for remodeling the ductus arteriosus

Nature Medicine volume 8, pages 91–92 (2002)Cite this article

To the editor

Expression of Pgdh could not be detected by northern-blot analysis of RNA prepared from the lung and liver of mice homozygous for the mutated Pgdh allele (Fig. 1b). The Pgdh−/− pups failed to survive the perinatal period (Table 1), and analysis of a series of litters indicated that mice lacking PGDH die 12–48 hours after birth. Necropsies of the Pgdh−/− pups revealed a patent DA (PDA) of similar diameter to that of a full-term fetus (Fig. 1c). Histological analysis of the DA of the Pgdh−/− pups confirmed this observation. No changes consistent with remodeling of the vessel were detected (data not shown). In contrast, numerous changes characteristic of the remodeling of this vessel, including lifting of endothelial cells, fragmentation of the elastic lamina, migration of smooth-muscle cells and obstruction of the lumen by intimal thickening, could be observed in the DAs of wild-type pups4. The major organs of the Pgdh−/− mice had morphological and histological changes that were consistent with death from congestive heart failure. This suggests that failure of the DA to close leads to a left-to-right shunt of blood across the DA, resulting in the development of congestive heart failure due to left-ventricle overload and exposure of the right ventricle to arterial pressures.

Table 1 Observed genotype ratios from Pgdh+/− heterozygous crosses
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Figure 1: Generation and characterization of mice lacking 15-hydroxyprostaglandin dehydrogenase (PGDH).

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA

    Kenneth G. Coggins, Ann Latour, Mytrang S. Nguyen & Beverly H. Koller

  2. Division of Nephrology, Department of Medicine Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina, USA

    Laurent Audoly & Thomas M. Coffman

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  1. Kenneth G. Coggins
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  2. Ann Latour
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Coggins, K., Latour, A., Nguyen, M. et al. Metabolism of PGE2 by prostaglandin dehydrogenase is essential for remodeling the ductus arteriosus. Nat Med 8, 91–92 (2002). https://doi.org/10.1038/nm0202-91

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