Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
| Autor: | Gregory B. Waypa, Keng Jin Lee, Mary E. Robbins, Herminio J. Cardona, Joann M. Taylor, Sara K. Berkelhamer, Marta Perez, Kathryn N. Farrow |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell signaling Protein Expression lcsh:Medicine 030204 cardiovascular system & hematology Signal transduction Pathology and Laboratory Medicine Diagnostic Radiology chemistry.chemical_compound Mice 0302 clinical medicine Medicine and Health Sciences Pulmonary Arteries lcsh:Science Cyclic GMP Lung Bronchopulmonary Dysplasia Hyperoxia Multidisciplinary Radiology and Imaging Animal Models Arteries Pulmonary Imaging 3. Good health Chemistry medicine.anatomical_structure Experimental Organism Systems Physical Sciences medicine.symptom Anatomy Research Article Chemical Elements medicine.medical_specialty Cell biology Sildenafil Imaging Techniques Hypertension Pulmonary Mouse Models Pulmonary Artery Vascular Remodeling Research and Analysis Methods Sildenafil Citrate 03 medical and health sciences Signs and Symptoms Model Organisms Diagnostic Medicine Internal medicine medicine.artery medicine Gene Expression and Vector Techniques Animals Molecular Biology Techniques Cyclic guanosine monophosphate Molecular Biology Cyclic Nucleotide Phosphodiesterases Type 5 Molecular Biology Assays and Analysis Techniques Hypertrophy Right Ventricular business.industry lcsh:R Biology and Life Sciences Neonates Phosphodiesterase 5 Inhibitors medicine.disease Pulmonary hypertension Mice Inbred C57BL Oxygen Pulmonary Alveoli Disease Models Animal 030104 developmental biology Endocrinology Bronchopulmonary dysplasia chemistry Animals Newborn Guanylate Cyclase Pulmonary artery cGMP signaling Room air distribution Cardiovascular Anatomy Blood Vessels lcsh:Q business Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 8, p e0180957 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease. C57BL/6 mice were placed in room air or 75% O2 within 24h of birth for 14d, followed by recovery in room air for an additional 7 days (21d). Additional pups were treated with either vehicle or sildenafil for 7d during room air recovery. Mean alveolar area, pulmonary artery (PA) medial wall thickness (MWT), RVH, and vessel density were evaluated at 21d. PA protein from 21d animals was analyzed for soluble guanylate cyclase (sGC) activity, PDE5 activity, and cGMP levels. Neonatal hyperoxia exposure results in persistent alveolar simplification, RVH, decreased vessel density, increased MWT, and disrupted cGMP signaling despite a period of room air recovery. Delayed treatment with sildenafil during room air recovery is associated with improved RVH and decreased PA PDE5 activity, but does not have significant effects on alveolar simplification, PA remodeling, or vessel density. These data are consistent with clinical studies suggesting inconsistent effects of sildenafil treatment in infants with BPD-associated PH. |
| Databáze: | OpenAIRE |
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