scholarly journals Prostaglandin E-mediated molecular mechanisms driving remodeling of the ductus arteriosus

2015 ◽  
Vol 57 (5) ◽  
pp. 820-827 ◽  
Author(s):  
Utako Yokoyama
Keyword(s):  
Molecular Mechanisms ◽  
Ductus Arteriosus ◽  
Prostaglandin E

scholarly journals Molecular Mechanisms Underlying Remodeling of Ductus Arteriosus: Looking beyond the Prostaglandin Pathway

2021 ◽  
Vol 22 (6) ◽  
pp. 3238
Author(s):  
Ho-Wei Hsu ◽  
Ting-Yi Lin ◽  
Yi-Ching Liu ◽  
Jwu-Lai Yeh ◽  
Jong-Hau Hsu
Keyword(s):  
Adverse Effect ◽  
Clinical Management ◽  
Vascular Remodeling ◽  
Molecular Mechanisms ◽  
Surgical Intervention ◽  
Ductus Arteriosus ◽  
Clinical Problem ◽  
Cyclooxygenase Inhibitors ◽  
Medical Patients ◽  
Fetal Circulation

The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.

Prostaglandin E and the Ductus Arteriosus

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.

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

PEDIATRICS ◽  
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.

scholarly journals Identification of differentially regulated genes in human patent ductus arteriosus

2016 ◽  
Vol 241 (18) ◽  
pp. 2112-2118 ◽  
Author(s):  
Pratik Parikh ◽  
Haiqing Bai ◽  
Michael F Swartz ◽  
George M Alfieris ◽  
David A Dean
Keyword(s):  
Cultured Cells ◽  
Ductus Arteriosus ◽  
Coarctation Of The Aorta ◽  
Transient Transfection ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Prostaglandin E ◽  
Promoter Regions ◽  
Mrna Quantitation ◽  
Multiple Patients

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.

A novel approach to ductal spasm during percutaneous device occlusion of patent ductus arteriosus

2015 ◽  
Vol 26 (7) ◽  
pp. 1352-1358 ◽  
Author(s):  
Rik De Decker ◽  
George Comitis ◽  
Jenny Thomas ◽  
Elmarie van der Merwe ◽  
John Lawrenson
Keyword(s):  
Patent Ductus Arteriosus ◽  
Ductus Arteriosus ◽  
Prostaglandin E ◽  
Total Intravenous Anaesthesia ◽  
Intravenous Anaesthesia ◽  
Transcatheter Occlusion ◽  
Novel Approach ◽  
Complete Relaxation ◽  
Induction Of Anaesthesia ◽  
Patent Ductus

AbstractDuctal spasm is a rare yet important complication of device occlusions of patent ductus arteriosus. Spasm may result in failure of the procedure, under-sizing of the device, or embolisation of the implanted device as the spasm resolves after the procedure. We describe a novel protocol that rapidly and completely reversed the spasm in eight prematurely born infants who experienced ductal spasm during cardiac catheterisations for patent ductus arteriosus occlusion.In total, eight infants born between 25 and 34 weeks of gestation presented for transcatheter patent ductus arteriosus occlusion between 13 and 87 months of age. All eight patients experienced ductal spasm either immediately before, during, or soon after induction of anaesthesia or only after entering the ductus arteriosus with a catheter. After detection of the spasm, the anaesthetist, in each case, changed the mode of anaesthesia from inhaled sevoflurane to total intravenous anaesthesia with propofol, reduced the inhaled oxygen fraction to 21%, and initiated a continuous intravenous infusion of prostaglandin E1.The first two steps (total intravenous anaesthesia and FiO2 0.21) resulted in only partial relaxation of the spasm. Complete relaxation was attained after intravenous prostaglandin E1 infusions of only 10–15 minutes’ duration. While maintaining this protocol, six ducti were successfully occluded and two were considered to be unsuitable for device occlusion and were referred for surgery.Ductal spasm during transcatheter occlusion may be reliably resolved and the procedure safely completed by a simple anaesthetic protocol, including the continuous infusion of intravenous prostaglandin E1.

scholarly journals Developmental Changes in Prostaglandin E 2 Receptor Subtypes in Porcine Ductus Arteriosus

Circulation ◽  
1999 ◽  
Vol 100 (16) ◽  
pp. 1751-1756 ◽  
Author(s):  
Mousumi Bhattacharya ◽  
Pierre Asselin ◽  
Pierre Hardy ◽  
Anne-Marie Guerguerian ◽  
Hitoshi Shichi ◽  
...  
Keyword(s):  
Ductus Arteriosus ◽  
Developmental Changes ◽  
Prostaglandin E ◽  
Receptor Subtypes

scholarly journals Interleukin-4 in the Generation of the AERD Phenotype: Implications for Molecular Mechanisms Driving Therapeutic Benefit of Aspirin Desensitization

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
John W. Steinke ◽  
Spencer C. Payne ◽  
Larry Borish
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Cell Types ◽  
Therapeutic Benefit ◽  
Interleukin 4 ◽  
Prostaglandin E ◽  
Aspirin Desensitization ◽  
Over Expression ◽  
Cysteinyl Leukotriene ◽  
Cox 2

Aspirin-exacerbated respiratory disease (AERD) is explained in part by over-expression of 5-lipoxygenase, leukotriene C4 synthase (LTC4S) and the cysteinyl leukotriene (CysLT) receptors (CysLT1 and 2), resulting in constitutive over-production of CysLTs and the hyperresponsiveness to CysLTs that occurs with aspirin ingestion. Increased levels of IL-4 have been found in the sinus mucosa and nasal polyps of AERD subjects. Previous studies demonstrated that IL-4 is primarily responsible for the upregulation of LTC4S by mast cells and the upregulation of CysLT1 and 2 receptors on many immune cell types. Prostaglandin E2 (PGE2) acts to prevent CysLT secretion by inhibiting mast cell and eosinophil activation. PGE2 concentrations are reduced in AERD reflecting diminished expression of cyclooxygenase (COX)-2. IL-4 can inhibit basal and stimulated expression of COX-2 and microsomal PGE synthase 1 leading to decreased capacity for PGE2 secretion. Thus, IL-4 plays an important pathogenic role in generating the phenotype of AERD. This review will examine the evidence supporting this hypothesis and describe a model of how aspirin desensitization provides therapeutic benefit for AERD patients.

scholarly journals PGE2-mediated cytoprotection in renal epithelial cells: evidence for a pharmacologically distinct receptor

1997 ◽  
Vol 273 (4) ◽  
pp. F507-F515 ◽  
Author(s):  
Thomas J. Weber ◽  
Terrence J. Monks ◽  
Serrine S. Lau
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Level ◽  
Binding Activity ◽  
Epithelial Cell Line ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Kinase C ◽  
Toxic Concentration ◽  
Ep Receptor ◽  
Responsive Element

Although the exact mechanism of prostaglandin E2(PGE2)-mediated cytoprotection has not been elucidated, its ability to induce cytoprotection in cell culture suggests this action occurs at the cellular level. The present studies were conducted to determine whether PGE2induces protection against 2,3,5-(trisglutathion- S-yl)-hydroquinone [2,3,5-(trisglutathion- S-yl)-HQ]-mediated cytotoxicity in a renal proximal tubule epithelial cell line (LLC-PK1) and to delineate the cellular and molecular mechanisms associated with this response. Pretreatment of LLC-PK1cells with 0.01–40 μM PGE2for 24 h fully protects against a moderately toxic concentration of 2,3,5-(trisglutathion- S-yl)-HQ. PGE2-mediated cytoprotection is observed in cells pretreated at pH 7.4 but not at pH 7.8. However, cytoprotection is observed in LLC-PK1cells pretreated with the PGE2analog, 11-deoxy-16,16-dimethyl PGE2(DDM-PGE2) but not with the PGE2receptor [E-prostanoid (EP)] agonists 17-phenyltrinor PGE2(EP1), 11-deoxy PGE1(EP2/EP4), sulprostone (EP1/EP3), PGE1, or PGA2. 12- O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C (PKC), also induces cytoprotection, supporting a role for this pathway in the cytoprotective response. PGE2, DDM-PGE2, and TPA all induce the binding of nuclear proteins to a TPA responsive element (TRE), whereas analogs that did not induce cytoprotection (PGE1, 17-phenyltrinor PGE2, sulprostone) were without effect. DDM-PGE2- and TPA-mediated cytoprotection and TRE binding activity are inhibited by N-(2{[3-(4-bromophenyl)-2-propenyl]-amino}-ethyl)-5-isoquinolinesulfonamide (H-89), a PKC inhibitor. These data suggest that cytoprotection by PGE2and DDM-PGE2in LLC-PK1cells is mediated by a PKC-coupled receptor, which is pharmacologically distinct from the presently classified EP receptor subtypes.

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