Prenatal treprostinil improves pulmonary arteriolar hypermuscularization in the rabbit model of congenital diaphragmatic hernia.

Autor: De Bie FR; Unit of Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Belgium., Regin Y; Unit of Woman and Child, Department of Development and Regeneration, KU Leuven, Belgium., Dubois A; Unit of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium., Scuglia M; Unit of Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Belgium., Arai T; Unit of Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Belgium., Muylle E; Unit of Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Belgium., Basurto D; Unit of Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Belgium., Regin M; Research Group Reproduction and Genetics, Vrije Universiteit Brussel, Belgium., Croubels S; Department of Pathobiology, Pharmacology and Zoological Medicine, Laboratory of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium., Cherlet M; Department of Pathobiology, Pharmacology and Zoological Medicine, Laboratory of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium., Partridge EA; Center for Fetal Research, The Children's Hospital of Philadelphia, United States., Allegaert K; Unit of Woman and Child, Department of Development and Regeneration, KU Leuven, Belgium; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; Department of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands., Russo FM; Unit of Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Belgium; Division of Obstetrics and Gynecology, University Hospitals Leuven, Belgium., Deprest JA; Unit of Urogenital, Abdominal and Plastic Surgery, Department of Development and Regeneration, KU Leuven, Belgium; Division of Obstetrics and Gynecology, University Hospitals Leuven, Belgium; Institute for Women's Health, University College London, United Kingdom. Electronic address: jan.deprest@uzleuven.be.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Jan; Vol. 170, pp. 115996. Date of Electronic Publication: 2023 Dec 12.
DOI: 10.1016/j.biopha.2023.115996
Abstrakt: Congenital diaphragmatic hernia (CDH) is a congenital malformation characterized by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Pulmonary hypertension represents the major cause of neonatal mortality and morbidity. Prenatal diagnosis allows assessment of severity and selection of foetal surgery candidates. We have shown that treprostinil, a prostacyclin analogue with an anti-remodelling effect, attenuates the relative hypermuscularization of the pulmonary vasculature in rats with nitrofen-induced CDH. Here we confirm these observations in a large animal model of surgically-created CDH. In the rabbit model, subcutaneous maternal administration of treprostinil at 150 ng/kg/min consistently reached target foetal concentrations without demonstrable detrimental foetal or maternal adverse effects. In pups with CDH, prenatal treprostinil reduced pulmonary arteriolar proportional medial wall thickness and downregulated inflammation and myogenesis pathways. No effect on alveolar morphometry or lung mechanics was observed. These findings provide further support towards clinical translation of prenatal treprostinil for CDH.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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