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Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice
Min Yee1, E David Cohen1, Jeannie Haak1
1The Department of Pediatrics, School of Medicine and Dentistry, The University of Rochester, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA.
Insights
Premature birth oxygen exposure may increase COVID-19 severity by altering SARS-CoV-2 receptors in the lungs. This finding may explain why elderly individuals and those with comorbidities face greater risks.
Area of Science:
- Pulmonary Medicine
- Neonatology
- Infectious Diseases
Background:
- COVID-19 severity is higher in the elderly and those with comorbidities.
- Preterm birth survivors exposed to neonatal hyperoxia may face increased risk for severe respiratory viral infections, including COVID-19.
Purpose of the Study:
- To investigate the impact of neonatal hyperoxia on the expression of SARS-CoV-2 receptors (ACE2 and TMPRSS2) in the developing mouse lung.
- To explore the potential protective role of mitoTEMPO against hyperoxia-induced changes in these receptors.
Main Methods:
- Mice were exposed to hyperoxia or normoxia from birth.
- Expression of ACE2 and TMPRSS2 was assessed in lung tissues at different ages.
- MitoTEMPO was administered to assess its effect on hyperoxia-induced changes.
Main Results:
- Neonatal hyperoxia led to altered expression patterns of ACE2 and TMPRSS2 in mouse lungs.
- ACE2 was detected in Club cells and endothelial cells at birth, and later in AT2 cells.
- Hyperoxia stimulated ACE2 expression in Club and AT2 cells by 2 months and TMPRSS2 expression in the lung.
- MitoTEMPO treatment blocked the hyperoxia-induced increase in SARS-CoV-2 receptor expression and reduced oxidative stress.
Conclusions:
- Neonatal hyperoxia alters the age-dependent expression of SARS-CoV-2 receptors in the mouse lung.
- These alterations may contribute to increased susceptibility to severe COVID-19, particularly in preterm infants and the elderly.
- MitoTEMPO shows potential in mitigating hyperoxia-induced lung damage and receptor changes.
Abstract:
The severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen (hyperoxia) at birth increases the severity of respiratory viral infections. Hyperoxia at birth increases the severity of influenza A virus infections in adult mice by reducing the number of alveolar epithelial type 2 (AT2) cells. Since AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), their expression should decline as AT2 cells are depleted by hyperoxia. Instead, ACE2 was detected in airway Club cells and endothelial cells at birth, and then AT2 cells at one year of age. Neonatal hyperoxia stimulated expression of ACE2 in Club cells and in AT2 cells by 2 months of age. It also stimulated expression of TMPRSS2 in the lung. Increased expression of SARS-CoV-2 receptors was blocked by mitoTEMPO, a mitochondrial superoxide scavenger that reduced oxidative stress and DNA damage seen in oxygen-exposed mice. Our finding that hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in mice helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities.
