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Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition
Ravi Goyal1, Dipali Goyal1, Lawrence D Longo1
1Center for Perinatal Biology, Division of Basic Sciences, Loma Linda University, Loma Linda, California.
Insights
New research reveals key molecular pathways involved in the closure of the ductus arteriosus (DA) in newborns. Understanding these pathways could lead to improved treatments for patent ductus arteriosus (PDA) in premature infants.
Area of Science:
- Neonatal physiology
- Cardiovascular development
- Molecular biology
Background:
- Patent ductus arteriosus (PDA) is a common congenital heart defect in newborns, especially preterm infants.
- Current treatments for PDA have limited efficacy (70-80%) and potential side effects.
- Novel molecular pathways regulating ductus arteriosus (DA) maturation and closure require investigation.
Purpose of the Study:
- To explore molecular pathways involved in DA maturation and closure.
- To test the hypothesis that DA development involves significant mRNA expression alterations.
Main Methods:
- Oligonucleotide microarray analysis of mRNA from DA and aorta.
- Comparison of gene expression in premature fetuses, near-term fetuses, and newborn lambs.
- Identification of genes specifically involved in DA maturation.
Main Results:
- Significant changes observed in wingless-integrin1, thrombospondin 1, and nitric oxide synthase signaling pathways.
- Alterations noted in receptor activator of nuclear factor-kappa B and retinoic acid receptor activation pathways.
- Identification of specific mRNA expression changes during DA maturation.
Conclusions:
- Identified molecular pathways are crucial for DA development and postnatal closure.
- These pathways warrant further investigation for potential therapeutic targets.
- Findings may lead to improved treatments for PDA in premature infants.
Background:
Patent ductus arteriosus (PDA) in the newborn is the most common congenital heart anomaly and is significantly more common in preterm infants. Contemporary pharmacological treatment is effective in only 70-80% of the cases. Moreover, indomethacin or ibuprofen, which are used to close a PDA may be accompanied by serious side effects in premature infants. To explore the novel molecular pathways, which may be involved in the maturation and closure of the ductus arteriosus (DA), we used fetal and neonatal sheep to test the hypothesis that maturational development of DA is associated with significant alterations in specific mRNA expression.
Methods:
We conducted oligonucleotide microarray experiments on the isolated mRNA from DA and ascending aorta from three study groups (premature fetus-97 ± 0 d, near-term fetus-136 ± 0.8 d, and newborn lamb-12 ± 0 h). We compared the alterations in mRNA expression in DA and aorta to identify genes specifically involved in DA maturation.
Results:
Results demonstrate significant changes in wingless-integrin1, thrombospondin 1, receptor activator of nuclear factor-kappa B, nitric oxide synthase, and retinoic acid receptor activation signaling pathways.
Conclusion:
We conclude that these pathways may play an important role during both development and postnatal DA closure and warrant further investigation.
