**3. Conclusion**

Ductal closure occurs in two phases. In full-term newborns, the first few hours after birth see acute and functional closure as a result of smooth muscle contraction of the DA, which is triggered by an increase in oxygen tension and a decline in levels of circulating PGE2. Importantly, prior to this, anatomical vascular remodelling occurs under the control of highly conserved yet complex molecular mechanisms. This remodelling requires a specific sequence of processes, which includes the differentiation of vascular SMCs and endothelial cells, the accumulation of extracellular matrix, vascular SMC migration into the subendothelial region, impaired elastogenesis, and eventually fibrotic changes due to apoptosis and necrosis. Recent advances in high-throughput genetic screening for human diseases and genetically manipulated animal models of PDA have facilitated the identification of pathways and genes involved in development and closure of the DA. As seen in the PGE2-EP4-cAMP signal pathway as well as in the oxygen and calcium channels, multiple vasoreactive stimulations can serve as an important modulator of vascular remodelling of the DA. In this regard, endothelin-1, nitric oxide, and other vasoreactive factors in the DA that we have not discussed here in detail may play a role in vascular remodelling of the DA. Thus, it is reasonable to infer that endothelial cells in the DA may also play an important role in the differentiation of vascular SMCs, which are considered to be a pivotal cellular structure in the pathogenesis of PDA. In addition to its role in controlling vascular tone in the functional closure of the DA, the vascular remodelling of the DA is now attracting considerable attention as a target for novel therapeutic strategies for patients with PDA and DA-dependent cardiac anomalies.
