Project description:The ductus arteriosus constricts after birth or hatching and eventually closes to terminate embryonic circulation. Chicken embryos have two long ductus arteriosus. Then the pulmonary artery-sided and descending aorta-sided ductus arteriosus have distinct functional characteristics, such as oxygen responsiveness. We used microarrays to elucidate the difference between the pulmonary artery-sided and descending aorta-sided ductus arteriosus in their transcriptional profiles.
Project description:Patent ductus arteriosus (PDA) is the third most common congenital heart disease and resulted from the persistence of ductal patency after birth. Ductus arteriosus closure involves functional and structural remodeling, controlled by many factors. The closure-related human plasma proteins are unknown. Here we for the first time demonstrate six key differential plasma proteins in the human PDA patients using proteomic technology and present a model to illustrate the constriction and closure of ductus arteriosus. We found that permanent closure might be regulated by the proteins related to platelet activation and coagulation cascades, complement mannan-binding-lectin, and other systemic signaling pathways. Our findings indicate that the differential proteins involved in these pathways may play key roles in the non-closure of the ductus arteriosus and may be developed as biomarkers for diagnosis. All those findings may be served as the basis of understanding the etiology and pathogenesis of PDA.
Project description:Failure to close the ductus arteriosus immediately post-birth, patent ductus arteriosus (PDA), accounts for up to 10% of all congenital heart defects. Despite significant advances in PDA management options, including pharmacological treatment targeting the prostaglandin pathway, a proportion of patients fail to respond and must undergo surgical intervention. Thus, further refinement of the cellular and molecular mechanisms that govern vascular remodeling of this vessel is required. As anticipated, single-cell RNA sequencing on the ductus arteriosus in mouse embryos at E18.5, P0.5, and P5, revealed broad transcriptional alterations in the endothelial, smooth muscle, and fibroblast cell compartments. After close evaluation of the transcriptomic dataset, we predicted that vimentin might be required for complete closure of the vessel. Subsequent studies demonstrated that, in fact, mice with genetic deletion of vimentin fail to fully remodel the ductus arteriosus. Through single-cell RNA-sequencing and by tracking closure of the ductus arteriosus postnatally in mice, we uncovered the unexpected contribution of vimentin in driving complete closure of the ductus arteriosus potentially through regulation of the Notch signaling pathway.
Project description:The ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life. We used microarrays to compare ductus arteriosis (DA) and aortic gene expression at a single time point (day 19 of gestation, which is the day of expected delivery).
Project description:The transcriptional profiles of the aorta and the ductus arteriosus during development were compared. Experiment Overall Design: Total RNA samples were isolated from pooled tissues obtained from Wister rat embryos on embryonic day 19 and 21, and from neonates on the day of birth (n>=120). The RNA was converted to biotin-labeled cRNA, which was hybridized to Affymetrix RG_U34A microarray. The hybridization experiments were performed in duplicate.
Project description:The effects of retinoic acid/vitamin A signal on the transcriptional profile of the ductus arteriosus during development were examined. Experiment Overall Design: Total RNA samples were isolated from pooled tissues obtained from Wister rat embryos on embryonic day 19 and 21, and from neonates on the day of birth (n>=120). The RNA was converted to biotin-labeled cRNA, which was hybridized to Affymetrix RG_U34A microarray. The hybridization experiments were performed in duplicate.
Project description: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 to 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.