Endothelial adenosine monophosphate-activated protein kinase-alpha1 deficiency potentiates hyperoxia-induced experimental bronchopulmonary dysplasia and pulmonary hypertension

Ahmed Elsaie, Renuka T. Menon, Amrit K. Shrestha, Sharada H. Gowda, Nidhy P. Varghese, Roberto J. Barrios, Cynthia L. Blanco, Girija G. Konduri, Binoy Shivanna

Producción científica: Articlerevisión exhaustiva

6 Citas (Scopus)

Resumen

Bronchopulmonary dysplasia and pulmonary hypertension, or BPD-PH, are serious chronic lung disorders of prematurity, without curative therapies. Hyperoxia, a known causative factor of BPD-PH, activates adenosine monophosphate-activated protein kinase (AMPK) α1 in neonatal murine lungs; however, whether this phenomenon potentiates or mitigates lung injury is unclear. Thus, we hypothesized that (1) endothelial AMPKα1 is necessary to protect neonatal mice against hyperoxia-induced BPD-PH, and (2) AMPKα1 knockdown decreases angiogenesis in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs). We performed lung morphometric and echocardiographic studies on postnatal day (P) 28 on endothelial AMPKα1-sufficient and-deficient mice exposed to 21% O2 (normoxia) or 70% O2 (hyperoxia) from P1–P14. We also performed tubule formation assays on control-or AMPKα1-siRNA transfected HPMECs, exposed to 21% O2 or 70% O2 for 48 h. Hyperoxia-mediated alveolar and pulmonary vascular simplification, pulmonary vascular remodeling, and PH were significantly amplified in endothelial AMPKα1-deficient mice. AMPKα1 siRNA knocked down AMPKα1 expression in HPMECs, and decreased their ability to form tubules in normoxia and hyperoxia. Furthermore, AMPKα1 knockdown decreased proliferating cell nuclear antigen expression in hyperoxic conditions. Our results indicate that AMPKα1 is required to reduce hyperoxia-induced BPD-PH burden in neonatal mice, and promotes angiogenesis in HPMECs to limit lung injury.

Idioma originalEnglish (US)
Número de artículo1913
PublicaciónAntioxidants
Volumen10
N.º12
DOI
EstadoPublished - dic 2021

ASJC Scopus subject areas

  • Food Science
  • Molecular Biology
  • Physiology
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

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