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Bronchopulmonary Dysplasia and Pulmonary Hypertension. The Role of Smooth Muscle adh5.
Raffay, Thomas M; Bonilla-Fernandez, Koby; Jafri, Anjum; Sopi, Ramadan B; Smith, Laura A; Cui, Feifei; O'Reilly, Maureen; Zhang, Rongli; Hodges, Craig A; MacFarlane, Peter M; Deutsch, Gail; Martin, Richard J; Gaston, Benjamin.
Afiliación
  • Raffay TM; Division of Neonatology, Department of Pediatrics, and.
  • Bonilla-Fernandez K; Division of Pediatric Pulmonology, Department of Pediatrics, University Hospitals Rainbow Babies & Children's Hospital and Case Western Reserve University School of Medicine, Case Western Reserve University, Cleveland, Ohio.
  • Jafri A; San Juan Bautista School of Medicine, Caguas, Puerto Rico.
  • Sopi RB; Division of Pediatric Pulmonology, Department of Pediatrics, University Hospitals Rainbow Babies & Children's Hospital and Case Western Reserve University School of Medicine, Case Western Reserve University, Cleveland, Ohio.
  • Smith LA; Division of Neonatology, Department of Pediatrics, and.
  • Cui F; Department of Pediatrics, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana.
  • O'Reilly M; Division of Pediatric Pulmonology, Department of Pediatrics, University Hospitals Rainbow Babies & Children's Hospital and Case Western Reserve University School of Medicine, Case Western Reserve University, Cleveland, Ohio.
  • Zhang R; Division of Neonatology, Department of Pediatrics, and.
  • Hodges CA; Department of Medicine, Institute for Transformative Molecular Medicine, Cardiovascular Research Institute, University Hospitals Cleveland Medical Center, and.
  • MacFarlane PM; Department of Genetics, Case Western Reserve University, Cleveland, Ohio; and.
  • Deutsch G; Division of Neonatology, Department of Pediatrics, and.
  • Martin RJ; Department of Pathology, Seattle Children's Hospital & University of Washington, Seattle, Washington.
  • Gaston B; Division of Neonatology, Department of Pediatrics, and.
Am J Respir Cell Mol Biol ; 65(1): 70-80, 2021 07.
Article en En | MEDLINE | ID: mdl-33780653
Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification, airway hyperreactivity, and pulmonary hypertension. In our BPD model, we have investigated the metabolism of the bronchodilator and pulmonary vasodilator GSNO (S-nitrosoglutathione). We have shown the GSNO catabolic enzyme encoded by adh5 (alcohol dehydrogenase-5), GSNO reductase, is epigenetically upregulated in hyperoxia. Here, we investigated the distribution of GSNO reductase expression in human BPD and created an animal model that recapitulates the human data. Blinded comparisons of GSNO reductase protein expression were performed in human lung tissues from infants and children with and without BPD. BPD phenotypes were evaluated in global (adh5-/-) and conditional smooth muscle (smooth muscle/adh5-/-) adh5 knockout mice. GSNO reductase was prominently expressed in the airways and vessels of human BPD subjects. Compared with controls, expression was greater in BPD smooth muscle, particularly in vascular smooth muscle (2.4-fold; P = 0.003). The BPD mouse model of neonatal hyperoxia caused significant alveolar simplification, airway hyperreactivity, and right ventricular and vessel hypertrophy. Global adh5-/- mice were protected from all three aspects of BPD, whereas smooth muscle/adh5-/- mice were only protected from pulmonary hypertensive changes. These data suggest adh5 is required for the development of BPD. Expression in the pulmonary vasculature is relevant to the pathophysiology of BPD-associated pulmonary hypertension. GSNO-mimetic agents or GSNO reductase inhibitors, both of which are currently in clinical trials for other conditions, could be considered for further study in BPD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alcohol Deshidrogenasa / Displasia Broncopulmonar / Miocitos del Músculo Liso / Hipertensión Pulmonar / Músculo Liso Vascular Límite: Animals / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Am J Respir Cell Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alcohol Deshidrogenasa / Displasia Broncopulmonar / Miocitos del Músculo Liso / Hipertensión Pulmonar / Músculo Liso Vascular Límite: Animals / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Am J Respir Cell Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos