Identification of differentially regulated genes in human patent ductus arteriosus

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 ΔΔCt 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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Prostaglandin Infusion in Neonate With Severe Coarctation of the Aorta With Closed Ductus Arteriosus—A Case Report and Review of the Literature

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135118799635 ◽

2019 ◽

Vol 11 (4) ◽

pp. NP239-NP243

Author(s):

Neha Bansal ◽

Preetha L. Balakrishnan ◽

Sanjeev Aggarwal

Keyword(s):

Surgical Repair ◽

Ductus Arteriosus ◽

Coarctation Of The Aorta ◽

Dose Dependence ◽

Spontaneous Closure ◽

Prostaglandin E ◽

Review Of The Literature ◽

Aortic Isthmus ◽

Ductal Tissue ◽

Putative Mechanism

We report the case of a premature newborn diagnosed with coarctation of the aorta after spontaneous closure of ductus arteriosus who was successfully managed with prostaglandin E1 infusion until surgical repair could be performed. This case, together with a review of the literature, suggests an important role for prostaglandin in the management of coarctation even in the absence of a patent ductus arteriosus. The putative mechanism for the utility of prostaglandin infusion is that it may relieve the obstruction in neonates with severe coarctation by not only opening of the ductus but, in select cases, relaxing the ductal tissue encircling the aortic isthmus region. We also found a possible dose dependence of the efficacy of the prostaglandin infusion when the ductus is closed.

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Prostaglandin E2 in a preterm infant with coarctation of the aorta

BMJ Case Reports ◽

10.1136/bcr-2019-230910 ◽

2019 ◽

Vol 12 (9) ◽

pp. e230910 ◽

Cited By ~ 1

Author(s):

Bernadette Khodaghalian ◽

Nimish V Subhedar ◽

Ashish Chikermane

Keyword(s):

Surgical Intervention ◽

Ductus Arteriosus ◽

Coarctation Of The Aorta ◽

Preterm Neonates ◽

Term Therapy ◽

Prostaglandin E ◽

Aortic Blood Flow ◽

Aortic Constriction ◽

Extremely Preterm ◽

Extremely Preterm Infants

Prostaglandins are widely used in aortic coarctation to maintain ductal patency and preserve systemic perfusion until surgical intervention can be performed. Although the short-term use of prostaglandins to ameliorate aortic narrowing in neonates with a closed ductus has been reported, it has not been described as a longer term therapy in extremely preterm neonates. A 27-week gestation baby weighing 560 g presented at 40 days of age with coarctation and a closed ductus arteriosus. He was successfully treated with a 7-week course of prostaglandin E2 therapy because surgical intervention was not deemed feasible in view of his size. Treatment resulted in a relaxation of the aortic constriction and improvement in aortic blood flow velocity profile, highlighting the value of long-term prostaglandin therapy in this population and supporting the hypothesis that the presence of ductal tissue contributes to the development of juxtaductal aortic constriction in some extremely preterm infants.

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Effectiveness of Prostaglandin E 1 in Relieving Obstruction in Coarctation of the Aorta Without Opening the Ductus Arteriosus

Pediatric Cardiology ◽

10.1007/s00246-003-0549-5 ◽

2004 ◽

Vol 25 (1) ◽

pp. 49-52 ◽

Cited By ~ 17

Author(s):

L. Liberman ◽

W. M. Gersony ◽

P. A. Flynn ◽

J. J. Lamberti ◽

R. S. Cooper ◽

...

Keyword(s):

Ductus Arteriosus ◽

Coarctation Of The Aorta ◽

Prostaglandin E

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Overexpression of miR-340-5p Inhibits Skin Fibroblast Proliferation by Targeting Kruppel-like Factor 2

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190725112304 ◽

2019 ◽

Vol 20 (13) ◽

pp. 1147-1154 ◽

Cited By ~ 2

Author(s):

Ling Chen ◽

Qian Li ◽

Xun Lu ◽

Xiaohua Dong ◽

Jingyun Li

Keyword(s):

Gene Ontology ◽

Skin Fibroblast ◽

Kegg Pathway ◽

Normal Skin ◽

Skin Fibroblasts ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Fibroblast Proliferation ◽

Pathway Analyses ◽

Normal Skin Fibroblast

Objective: MicroRNA (miR)-340-5p has been identified to play a key role in several cancers. However, the function of miR-340-5p in skin fibroblasts remains largely unknown. Methods: Gain of function experiments were performed by infecting normal skin fibroblast cells with a lentivirus carrying 22-bp miR-340-5p. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. To uncover the mechanisms, mRNA-seq was used. Differentially expressed mRNAs were further determined by Gene Ontology and KEGG pathway analyses. The protein levels were analysed by Western blotting. A dual-luciferase reporter assay was used to detect the direct binding of miR-340-5p with the 3'UTR of Kruppel-like factor 2 (KLF2). Results: MiR-340-5p lentivirus infection suppressed normal skin fibroblast proliferation. The mRNAseq data revealed that 41 mRNAs were differentially expressed, including 22 upregulated and 19 downregulated transcripts in the miR-340-5p overexpression group compared with those in the control group. Gene Ontology and KEGG pathway analyses revealed that miR-340-5p overexpression correlated with the macromolecule biosynthetic process, cellular macromolecule biosynthetic process, membrane, and MAPK signalling pathway. Bioinformatics analysis and luciferase reporter assays showed that miR-340-5p binds to the 3'UTR of KLF2. Forced expression of miR-340-5p decreased the expression of KLF2 in normal skin fibroblasts. Overexpression of KLF2 restored skin fibroblast proliferation in the miR-340-5p overexpression group. Conclusion: This study demonstrates that miR-340-5p may suppress skin fibroblast proliferation, possibly through targeting KLF2. These findings could help us understand the function of miR-340-5p in skin fibroblasts. miR-340-5p could be a therapeutic target for preventing scarring.

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Increased Prevalence of Ventricular Septal Defect: Epidemic or Improved Diagnosis

PEDIATRICS ◽

10.1542/peds.83.2.200 ◽

1989 ◽

Vol 83 (2) ◽

pp. 200-203

Author(s):

Gerard R. Martin ◽

Lowell W. Perry ◽

Charlotte Ferencz

Keyword(s):

Ventricular Septal Defect ◽

Septal Defect ◽

Ductus Arteriosus ◽

Coarctation Of The Aorta ◽

Cardiovascular Malformations ◽

Ventricular Septal Defects ◽

Live Births ◽

Septal Defects ◽

Clinical Diagnoses ◽

Control Study

The Baltimore-Washington Infant Study is an ongoing case-control study of congenital cardiovascular malformations in infants in whom the clinical diagnoses have been confirmed by echocardiography, catheterization, surgery, or autopsy. An increase in the prevalence of ventricular septal defects was detected in 1,494 infants with congenital cardiovascular malformations between 1981 and 1984. The prevalence of congenital cardiovascular malformations increased from 3.6 to 4.5 per 1,000 live births (P<.025) and the prevalence of ventricular septal defect increased from 1.0 to 1.6 per 1,000 live births (P< .001). The increase in ventricular septal defects accounted for the total increase in congenital cardiovascular malformations. The prevalence of isolated ventricular septal defect increased from 0.67 to 1.17 per 1,000 live births (P<.001). The prevalence of ventricular septal defect with associated coarctation of the aorta, patent ductus arteriosus, atrial septal defect, and pulmonic stenosis did not change. The prevalence of ventricular septal defect diagnosed by catheterization, surgery, and autopsy did not change; however, defects diagnosed by echocardiography increased from 0.30 to 0.70 per 1,000 live births (P<.001). It is concluded that the reported increase in prevalence of ventricular septal defect is due to improved detection of small, isolated ventricular septal defects and that there is no evidence of an "epidemic."

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Prostaglandin E and the Ductus Arteriosus

Pediatrics in Review ◽

10.1542/pir.7.3.75 ◽

1985 ◽

Vol 7 (3) ◽

pp. 75-76

Keyword(s):

Smooth Muscle ◽

Seminal Fluid ◽

Ductus Arteriosus ◽

Active Material ◽

Crystalline Form ◽

Prostaglandin E ◽

Chemical Structures ◽

Soluble Acid ◽

Derivatives Of ◽

Widespread Interest

In 1936, Euler of Sweden identified in seminal fluid an active material that contracts smooth muscle; he named this lipid-soluble acid "prostaglandin." More than 20 years passed before the isolation in crystalline form of two prostaglandins, PGE1 and PGE1a, was accomplished. The elucidation of their chemical structures in 1962 by Bergstrom led to their biosynthesis in 1964. Few substances have generated more widespread interest in biologic circles than the prostaglandins. The prostaglandins are derivatives of fatty acids and have been detected in almost every tissue including the fetal ductus. The E-type prostaglandins are powerful vasodilators of nearly all arterioles by direct relaxation of vascular smooth muscle.

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Screening candidate microR-15a- IRAK2 regulatory pairs for predicting the response to Staphylococcus aureus-induced mastitis in dairy cows

Journal of Dairy Research ◽

10.1017/s0022029919000785 ◽

2019 ◽

Vol 86 (4) ◽

pp. 425-431 ◽

Cited By ~ 3

Author(s):

Zhi Chen ◽

Jingpeng Zhou ◽

Xiaolong Wang ◽

Yang Zhang ◽

Xubin Lu ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Differential Expression ◽

High Throughput Sequencing ◽

Target Genes ◽

Interleukin 1 ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Expression Of Genes ◽

Chinese Holstein Cows ◽

Reporter Assays

AbstractWe established a mastitis model using exogenous infection of the mammary gland of Chinese Holstein cows with Staphylococcus aureus and extracted total RNA from S. aureus-infected and healthy mammary quarters. Differential expression of genes due to mastitis was evaluated using Affymetrix technology and results revealed a total of 1230 differentially expressed mRNAs. A subset of affected genes was verified via Q-PCR and pathway analysis. In addition, Solexa high-throughput sequencing technology was used to analyze profiles of miRNA in infected and healthy quarters. These analyses revealed a total of 52 differentially expressed miRNAs. A subset of those results was verified via Q-PCR. Bioinformatics techniques were used to predict and analyze the correlations among differentially expressed miRNA and mRNA. Results revealed a total of 329 pairs of negatively associated miRNA/mRNA, with 31 upregulated pairs of mRNA and 298 downregulated pairs of mRNA. Differential expression of miR-15a and interleukin-1 receptor-associated kinase-like 2 (IRAK2), were evaluated by western blot and luciferase reporter assays. We conclude that miR-15a and miR-15a target genes (IRAK2) constitute potential miRNA–mRNA regulatory pairs for use as biomarkers to predict a mastitis response.

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Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000495556 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1389-1398 ◽

Cited By ~ 17

Author(s):

Lili Zhu ◽

Tingting Ren ◽

Zixin Zhu ◽

Mingliang Cheng ◽

Qiuju Mou ◽

...

Keyword(s):

Liver Fibrosis ◽

Cell Activation ◽

Stellate Cell ◽

Circular Rna ◽

Fine Tuning ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Circular Rnas ◽

G1 Arrest

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis.

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Prolonged Prostaglandin E1 Infusion: Histologic Effects on the Patent Ductus Arteriosus

PEDIATRICS ◽

10.1542/peds.67.6.816 ◽

1981 ◽

Vol 67 (6) ◽

pp. 816-819

Author(s):

Roger B. Cole ◽

Steven Abman ◽

Kalim U. Aziz ◽

Saroja Bharati ◽

Maurice Lev

Keyword(s):

Pulmonary Artery ◽

Prostaglandin E1 ◽

Mononuclear Cells ◽

Ductus Arteriosus ◽

Prostaglandin E ◽

Cavity Formation ◽

Prolonged Infusion ◽

Histologic Study ◽

Surgical Closure ◽

The Media

An infant with Ebstein's malformation of the tricuspid valve and severe pulmonic stenosis under-went a 39-day course of prostaglandin E1 infusion, and a histologic study of the ductus arteriosus was undertaken after autopsy. There were marked alterations in the ductal and juxtaductal structures following this prolonged infusion of prostaglandin E1. The internal elastic lamella of the ductus was disrupted in many areas. The media showed widespread areas of disruption with cavity formation. The adventitia adjacent to the junction of the ductus with the pulmonary artery was thickened and infiltrated with mononuclear cells. The nerve trunks in the adventitia were markedly infiltrated with mononuclear cells and showed cavitation as well as considerable surrounding edema. Mucopolysaccharides were increased throughout the ductus. These changes produced increased fragility of the ductal and juxtaductal structures, thus increasing the likelihood of spontaneous aneurysms and rupture, or of tearing or rupture at the aortic and pulmonary junctions at the time of surgical closure of the ductus. Unusual fragility of the ductus, pulmonary artery, and aorta has been observed during ligation of the ductus following prostaglandin E infusions lasting seven and ten days. Additionally, another patient who had received prostaglandin E infusion for six days demonstrated aneurysmal fullness to the ductus arteriosus at autopsy. The histologic findings and intraoperative experience in this study suggest that there may be a real danger of spontaneous neous or surgically related rupture of the ductus arteriosus after prolonged infusion of prostaglandins.

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Coarctation-like Physiology with Cerebral Arteriovenous Fistula

PEDIATRICS ◽

10.1542/peds.44.6.1024 ◽

1969 ◽

Vol 44 (6) ◽

pp. 1024-1028

Author(s):

P. B. Deverall ◽

J. F. N. Taylor ◽

G. S. Sturrock ◽

Eoin Aberdeen

Keyword(s):

Arteriovenous Fistula ◽

Aortic Arch ◽

Cardiac Failure ◽

Ductus Arteriosus ◽

Coarctation Of The Aorta ◽

Aortic Isthmus ◽

Obstructive Lesion ◽

Cerebral Arteriovenous Fistula ◽

Flow Through ◽

Reduced Flow

Hemodynamic signs of coarctation of the aorta were present in a neonate dying in cardiac failure. A cerebral arteriovenous fistula was found at autopsy. No obstructive lesion of the aortic arch was present. Development of the aortic isthmus may be impaired if diminished flow through this segment is present. Reduced flow may be present if most of the systemic output is diverted to a fistula proximal to the isthmus, distal systemic flow being maintained by flow from right-to-left through the ductus arteriosus. Spontaneous duct closure after birth may then be followed by a reduction in distal systemic flow, resulting in signs suggestive of coarctation.

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