07 Jun Vascular Biomarker Predicts Death or Pulmonary Morbidity in Premature Infants
MedicalResearch.com Interview with:
Jegen Kandasamy MD
Division of Neonatology
Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program
University of Alabama at Birmingham
MedicalResearch.com: What is the background for this study?
Response: Preterm infants, especially those that are born with a birth weight of 750 grams or less, are prone to a lung disease called bronchopulmonary dysplasia (BPD) because the development of lungs in these infants takes place in an environment that has more oxygen than that available in utero. Recently, pulmonary blood vessel growth and function has been hypothesized to play a causal role in the pathogenesis of BPD. Vascular endothelial cell function has been shown to affect hyperoxia-induced lung damage in animal studies. An important source of human vascular endothelial cells is the umbilical cord of newborn infants. These human umbilical venous endothelial cells (HUVEC) have been used to measure endothelial cell function in various diseases but never in diseases related to the newborn infants from whom they were derived.
In addition, the mitochondria in various cells in our body respond to oxygen toxicity by creating, as well as consuming, reactive oxygen species (ROS) that mediate most of the effects of oxygen-induced damage. Therefore, we designed this study to measure mitochondrial function in vascular endothelial cells obtained from the umbilical cords of prematurely born infants at the time of their birth. We then compared these mitochondrial functional measures between infants who later died or developed BPD versus those who survived without BPD.
MedicalResearch.com: What are the main findings?
Response: Our study found that endothelial cells obtained from infants who died or developed BPD had lower mitochondrial oxygen consumption, released higher amounts of reactive oxygen species and had increased damage of their mitochondrial DNA when compared to cells obtained from infants who survived without lung disease.
MedicalResearch.com: What should readers take away from your report?
Response: Through this study we have established a clear association between endothelial mitochondrial function and risk for prematurity-associated lung disease in newborn infants. Decreased endothelial bioenergetics and increased ROS generation were found to be strong predictors for increased risk of early death or lung disease in preterm infants. Therefore, these measurements could be used as biomarkers for predicting which prematurely born infant is at higher risk for the development of lung disease later in life. Such knowledge could enable us to identify such infants early in their neonatal period and institute additional therapeutic measures that could decrease their risk for lung disease later in life. In addition, we have also found that certain subsets of preterm infants (such as African-American infants) had more dysfunctional endothelial mitochondrial function when compared to others, suggesting that mitochondrial dysfunction could be especially important as a contributor to lung disease in some infants more than in others.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: This study throws up several possible avenues that are promising grounds for future research. Since venous endothelial mitochondrial function is now known to be linked with lung dysfunction and injury in preterm infants, the mechanistic reasons behind this association need further investigation. Endothelial mitochondrial dysfunction could impair angiogenesis in the growing lung by decreasing nitric oxide and growth factor availability in the microenvironment of the developing pulmonary vasculature. In addition, the increased ROS generation from these cells could lead to alveolar dysfunction, as well as increased fibrosis, both of which could lead to decreased function.
Since mitochondrial bioenergetic function is dependent on proteins that are derived from mitochondrial and nuclear gene expression, as well as interactions between these two genomes, variations in mitochondrial genetic haplotypes and their interaction with the nuclear genetic environment that could impair or modify mitochondrial response to hyperoxia need to be investigated. Additionally, mitochondrially-targeted therapeutic strategies that could be useful in modifying pulmonary mitochondrial dysfunction and could allow clinicians to safely decrease lung injury risk in preterm infants will also need to be investigated.
MedicalResearch.com: Is there anything else you would like to add?
Response: The University of Alabama at Birmingham is one of the few centers in the U.S. that combines strong mitochondrial and redox biology expertise with a capable and well-experienced team of neonatal physicians and lung development and injury researchers. This study was made possible through this rarely available combination of resources, including research infrastructure and personnel expertise.
Dr. Jegen Kandasamy indicates that their team has no relevant disclosures to make.
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Jegen Kandasamy , Nelida Olave , Scott W Ballinger , and Namasivayam Ambalavanan
https://doi.org/10.1164/rccm.201702-0353OC PubMed: 28485984
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