Kaohsiung Medical University, Taiwan
Scientific Tracks Abstracts: J Clin Exp Cardiolog
The ductus arteriosus (DA) is an artery indispensable in fetal circulation. PDA is a major cause of morbidity and mortality in premature infants, whereas persistent PDA is life-saving in newborns with DA-dependent CHDs. Therefore, elucidating molecular mechanisms underlying regulation of DA patency is an important field of vascular biology and translational research of pediatric cardiology. DA closure is a complex process including two mechanisms: functional and anatomical closures. Functional closure is a transient response mediated mainly by vasoconstriction caused by abrupt increase of oxygen tension and postnatal withdrawal of vasodilatory PGE2. Anatomical closure is a constitutive process of luminal obliteration characterized by intimal thickening, resulting in progressive DA vascular remodeling and permanent DA closure. Current clinical approach for management of DA patency is mainly targeted on the PGE/cAMP pathway. However, recent studies have shown that PGE can promote DA remodeling through EP4 receptor while maintaining DA vasodilation. Therefore, novel pharmacologic strategy regulating vaso-reactivity and remodeling would be helpful for management of functional and anatomic closure of DA. The purposes of this talk are to review the complex mechanisms regulating DA patency, and share our translational research of novel pharmacologic targets, including BNP, cGMP pathway and Notch signaling. An improved understanding of the mechanistic pathways regulating DA patency may yield novel or additional therapeutic strategies for patients with PDA and DA-dependent CHDs.