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Published on: October 19, 2013
Impaired cell-cell communication and axon guidance because of pulmonary hypoperfusion during postnatal alveolar
Debao Li1, Jing Wang2, Yuan Fang3
1Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, China.
Insights
Pulmonary hypoperfusion in children with congenital heart disease (CHD) or pulmonary hypertension (PH) alters alveolar development. This may explain why these children experience less severe COVID-19 outcomes.
Area of Science:
- Pediatric Cardiology
- Pulmonary Hypertension Research
- Developmental Biology
Background:
- Pulmonary hypoperfusion is prevalent in children with congenital heart diseases (CHDs) or pulmonary hypertension (PH), leading to pulmonary dysplasia.
- Children with CHDs or PH may exhibit milder COVID-19 clinical outcomes.
- Understanding pulmonary hypoperfusion's impact on alveolar development is crucial for improving care, especially during the COVID-19 pandemic.
Purpose of the Study:
- To investigate the effects of pulmonary hypoperfusion on postnatal alveolar development in a neonatal model.
- To explore potential therapeutic strategies for pulmonary hypoperfusion-induced alveolar dysplasia.
- To understand the implications for COVID-19 outcomes in affected children.
Main Methods:
- A neonatal pulmonary hypoperfusion model was established using pulmonary artery banding (PAB) surgery.
- Alveolar dysplasia was assessed via gross and histological examination.
- Transcriptomic analysis identified changes in cell-cell communication and axon guidance pathways.
Main Results:
- Pulmonary hypoperfusion significantly altered postnatal alveolar development, characterized by loss of cell-cell communication and axon guidance.
- Hyperactive cell cycle activity was observed under hypoperfusion conditions.
- The disruption of axon guidance may be linked to reduced inflammation and milder COVID-19 in these children.
Conclusions:
- Promoting cell-cell communication or supplementing guidance molecules could treat pulmonary hypoperfusion-induced alveolar dysplasia.
- Children with CHD or PH and pulmonary hypoperfusion may be less prone to severe COVID-19 cytokine storms.
- These findings offer insights into managing pulmonary function and COVID-19 in pediatric patients.
Background:
Pulmonary hypoperfusion is common in children with congenital heart diseases (CHDs) or pulmonary hypertension (PH) and causes adult pulmonary dysplasia. Systematic reviews have shown that some children with CHDs or PH have mitigated clinical outcomes with COVID-19. Understanding the effects of pulmonary hypoperfusion on postnatal alveolar development may aid in the development of methods to improve the pulmonary function of children with CHDs or PH and improve their care during the COVID-19 pandemic, which is characterized by cytokine storm and persistent inflammation.
Methods And Results:
We created a neonatal pulmonary hypoperfusion model through pulmonary artery banding (PAB) surgery at postnatal day 1 (P1). Alveolar dysplasia was confirmed by gross and histological examination at P21. Transcriptomic analysis of pulmonary tissues at P7(alveolar stage 2) and P14(alveolar stage 4) revealed that the postnatal alveolar development track had been changed due to pulmonary hypoperfusion. Under the condition of pulmonary hypoperfusion, the cell-cell communication and axon guidance, which both determine the final number of alveoli, were lost; instead, there was hyperactive cell cycle activity. The transcriptomic results were further confirmed by the examination of axon guidance and cell cycle markers. Because axon guidance controls inflammation and immune cell activation, the loss of axon guidance may explain the lack of severe COVID-19 cases among children with CHDs or PH accompanied by pulmonary hypoperfusion.
Conclusions:
This study suggested that promoting cell-cell communication or supplementation with guidance molecules may treat pulmonary hypoperfusion-induced alveolar dysplasia, and that COVID-19 is less likely to cause a cytokine storm in children with CHD or PH accompanied by pulmonary hypoperfusion.
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