Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants
| Autor: | Sunil Batlahally, Andrew Franklin, Pingping Chen, Shathiyah Kulandavelu, Karen C. Young, Rosemeire M. Kanashiro-Takeuchi, Karen K. Mestan, Augusto F. Schmidt, Eliana C. Martinez, Divya Keerthy, Lina A. Shehadeh, Andreas Damianos, Michael Freundlich, Jian Huang, Mayank Sharma, Merline Benny, Marissa DeFreitas, Ronald Zambrano, Joanne Duara, Shu Wu, Carolyn Abitbol |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cardiac function curve medicine.medical_specialty Hypertension Pulmonary lcsh:Medicine 030204 cardiovascular system & hematology Paediatric research urologic and male genital diseases Article 03 medical and health sciences 0302 clinical medicine Fibrosis Internal medicine mental disorders Humans Medicine Longitudinal Studies lcsh:Science Klotho Proteins Klotho Bronchopulmonary Dysplasia Glucuronidase Hyperoxia Multidisciplinary Lung business.industry lcsh:R Infant Newborn Fetal Blood medicine.disease Pulmonary hypertension female genital diseases and pregnancy complications 030104 developmental biology Endocrinology medicine.anatomical_structure Bronchopulmonary dysplasia Preclinical research Cord blood Female lcsh:Q medicine.symptom business Biomarkers Infant Premature |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-69296-1 |
| Popis: | Preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) have accelerated lung aging and poor long-term outcomes. Klotho is an antiaging protein that modulates oxidative stress, angiogenesis and fibrosis. Here we test the hypothesis that decreased cord Klotho levels in preterm infants predict increased BPD–PH risk and early Klotho supplementation prevents BPD-like phenotype and PH in rodents exposed to neonatal hyperoxia. In experiment 1, Klotho levels were measured in cord blood of preterm infants who were enrolled in a longitudinal cohort study. In experiment 2, using an experimental BPD–PH model, rat pups exposed to room air or hyperoxia (85% O2) were randomly assigned to receive every other day injections of recombinant Klotho or placebo. The effect of Klotho on lung structure, PH and cardiac function was assessed. As compared to controls, preterm infants with BPD or BPD–PH had decreased cord Klotho levels. Early Klotho supplementation in neonatal hyperoxia-exposed rodents preserved lung alveolar and vascular structure, attenuated PH, reduced pulmonary vascular remodeling and improved cardiac function. Together, these findings have important implications as they suggest that perinatal Klotho deficiency contributes to BPD–PH risk and strategies that preserve Klotho levels, may improve long-term cardiopulmonary outcomes in preterm infants. |
| Databáze: | OpenAIRE |
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