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Review
. 2018 Jun 25;19(7):1861.
doi: 10.3390/ijms19071861.

Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure

Yu-Chi Hung  1   2 , Jwu-Lai Yeh  3   4   5   6 , Jong-Hau Hsu  7   8   9   10
Affiliations
Review

Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure

Yu-Chi Hung et al. Int J Mol Sci. .

Abstract

The ductus arteriosus (DA) connects the main pulmonary artery and the aorta in fetal circulation and closes spontaneously within days after birth in normal infants. Abnormal patent DA (PDA) causes morbidities and mortality, especially in preterm infants. Closure of the DA is a complex interactive process involving two events: functional and anatomic closure. Functional closure by smooth muscle contraction was achieved through the regulatory factors of vaso-reactivity. These factors include oxygen sensing system, glutamate, osmolality, prostaglandin E₂, nitric oxide, and carbon monoxide. Anatomic closure by vascular remodeling involved several vascular components including endothelium, extracellular matrix, smooth muscle cells, and intraluminal blood cells. Despite advances in understanding of PDA pathogenesis, the molecular mechanism for regulation of DA closure is complex and not fully understood. In this article we review recent evidence regarding the molecular mechanisms of DA closure.

Keywords: ductus arteriosus; endothelial cells; extracellular matrix; smooth muscle cells; vascular remodeling.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pathways mediating functional closure of the ductus arteriosus. AC: adenylyl cyclase, cAMP: cyclic adenosine monophosphate, cGMP: cyclic guanosine monophosphate, EPs: PGE2 receptors, ET: endothelin, GluR1: glutamate inotropic receptor subunit 1, Mito: mitochondria, PGE2: prostaglandin E2, PKA: protein kinase A, PKG: protein kinase G, RA: retinoic acid, SMC: smooth muscle cells, TRPM3: transient receptor potential melastatin 3.
Figure 2
Figure 2
The diagram of anatomical closure of the ductus arteriosus. CS: chondroitin sulfate, EC: endothelial cells, ECM: extracellular matrix, IEL: internal elastic laminae, IL-15: Interleukin-15, Mono: monocyte, PDGF: platelet-derived growth factor, PGE2: prostaglandin E2, PLT: platelet, RA: retinoic acid, SMC: smooth muscle cells, TGF-β: transforming growth factor-β, VEGF: vascular endothelial growth factor.
See this image and copyright information in PMC

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