Current Perspectives on Pathobiology of the Ductus Arteriosus

Stoller, Jason Z.; DeMauro, Sara B.; Dagle, John M.; Reese, Jeff

doi:10.4172/2155-9880.s8-001

Cited by 33 publications

(52 citation statements)

References 162 publications

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“…In some cases, the DA fails to close resulting in a persistent left-to-right shunt, termed a patent ductus arteriosus (PDA). This condition may lead to a variety of complications including pulmonary hemorrhage, parenchymal lung disease, necrotizing enterocolitis, intraventricular hemorrhage, and death (2,12,40,53,64). Current pharmacological treatments for a PDA include indomethacin or ibuprofen, cyclooxygenase inhibitors that suppress PGE 2 (34).…”

mentioning

confidence: 99%

Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone

Shelton

Ector

Galindo

et al. 2014

Physiological Genomics

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mentioning

confidence: 99%

Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone

Shelton

Ector

Galindo

et al. 2014

Physiological Genomics

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“…1,7 Several others have a role in cellular growth and vascular remodeling. Several of these genes, including TFAP2B, PLA2, PTGER4, DLX1, and AGTR1, were found in our study to be either DA-enriched at the mRNA level or drove DA-enriched transgene expression when their promoters were cloned and used in transient transfection studies in cultured DA or aorta SMCs from patients.…”

Section: Discussionmentioning

confidence: 99%

“…7 Interestingly, the smooth muscle cells of ductus are derived entirely from cardiac neural crest cells, whereas smooth muscle cells of other vascular beds are mostly mesenchymal in origin. 8,9 While the aorta also is primarily derived from mesenchymal cells, some cells in the ascending aorta region also include a neural crest origin.…”

Section: Introductionmentioning

confidence: 99%

Identification of differentially regulated genes in human patent ductus arteriosus

Parikh

Bai

Swartz

et al. 2016

Exp Biol Med (Maywood)

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In order to identify differentially expressed genes that are specific to the ductus arteriosus, 18 candidate genes were evaluated in matched ductus arteriosus and aortic samples from infants with coarctation of the aorta. The cell specificity of the gene's promoters was assessed by performing transient transfection studies in primary cells derived from several patients. Segments of ductus arteriosus and aorta were isolated from infants requiring repair for coarctation of the aorta and used for mRNA quantitation and culturing of cells. Differences in expression were determined by quantitative PCR using the ÁÁCt method. Promoter regions of six of these genes were cloned into luciferase reporter plasmids for transient transfection studies in matched human ductus arteriosus and aorta cells. Transcription factor AP-2b and phospholipase A2 were significantly up-regulated in ductus arteriosus compared to aorta in whole tissues and cultured cells, respectively. In transient transfection experiments, Angiotensin II type 1 receptor and Prostaglandin E receptor 4 promoters consistently gave higher expression in matched ductus arteriosus versus aorta cells from multiple patients. Taken together, these results demonstrate that several genes are differentially expressed in ductus arteriosus and that their promoters may be used to drive ductus arteriosus-enriched transgene expression.

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“…During fetal life, the DA, responding to low oxygen tension, nitric oxide, and prostaglandin signaling, remains patent to shunt blood to the aorta, bypassing the immature, uninflated lungs. At birth, increasing blood oxygen content and decreasing prostaglandin levels stimulate DA closure, allowing appropriate perfusion of the newly inflated lungs (7,8,43,52). The timing of DA closure is tightly regulated.…”

Section: This Study Is the First To Elucidate A Mechanism By Which Sementioning

confidence: 99%

Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero

Hooper

Delaney

Streeter

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Use of selective serotonin reuptake inhibitors (SSRIs) is common during pregnancy. Fetal exposure to SSRIs is associated with persistent pulmonary hypertension of the newborn (PPHN); however, a direct link between the two has yet to be established. Conversely, it is well known that PPHN can be caused by premature constriction of the ductus arteriosus (DA), a fetal vessel connecting the pulmonary and systemic circulations. We hypothesized that SSRIs could induce in utero DA constriction. Using isolated vessels and whole-animal models, we sought to determine the effects of two commonly prescribed SSRIs, fluoxetine and sertraline, on the fetal mouse DA. Cannulated vessel myography studies demonstrated that SSRIs caused concentration-dependent DA constriction and made vessels less sensitive to prostaglandin-induced dilation. Moreover, in vivo studies showed that SSRI-exposed mice had inappropriate DA constriction in utero. Taken together, these findings establish that SSRIs promote fetal DA constriction and provide a potential mechanism by which SSRIs could contribute to PPHN. mouse; ductus arteriosus; SSRI; fluoxetine; sertraline; serotonin; PPHN NEW & NOTEWORTHY This study is the first to elucidate a mechanism by which serotonin reuptake inhibitors (SSRIs) alter ductus arteriosus tone. It also puts forth the notion that SSRIs may contribute to persistent pulmonary hypertension of the newborn by causing premature fetal ductus constriction.THE DUCTUS ARTERIOSUS (DA) is an essential fetal vessel connecting the pulmonary and systemic circulations. During fetal life, the DA, responding to low oxygen tension, nitric oxide, and prostaglandin signaling, remains patent to shunt blood to the aorta, bypassing the immature, uninflated lungs. At birth, increasing blood oxygen content and decreasing prostaglandin levels stimulate DA closure, allowing appropriate perfusion of the newly inflated lungs (7,8,43,52). The timing of DA closure is tightly regulated. If the DA fails to close (patent DA), serious consequences including pulmonary hemorrhage, parenchymal lung disease, intraventricular hemorrhage, and death can ensue. Conversely, premature DA constriction in utero is also undesirable and can lead to life-threatening conditions, including right ventricular hypertrophy, functional pulmonary atresia, absent pulmonary valve syndrome, hydrops fetalis, and persistent pulmonary hypertension of the newborn (PPHN) (18,20,23,31,32).PPHN is a disorder characterized by sustained elevated pulmonary vascular resistance (PVR). During fetal life, PVR is high due to a number of factors, including mechanical compression of the pulmonary arterioles by fluid-filled alveoli, low fetal oxygen tension, low levels of vasodilators (prostacyclin, nitric oxide), and elevated levels of vasoconstrictors (endothelin-1, thromboxane) (37). At birth, PVR should fall to facilitate a smooth transition from fetal to extrauterine life. However, in some cases, the pulmonary vasculature fails to relax, causing PPHN, a disorder accompanied by hypoxemia and right-...

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Current Perspectives on Pathobiology of the Ductus Arteriosus

Cited by 33 publications

References 162 publications

Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone

Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone

Identification of differentially regulated genes in human patent ductus arteriosus

Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero

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