scholarly journals In vivo intrabursal administration of bioactive lipid sphingosine-1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome

2017 ◽  
Vol 23 (6) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Di Pietro ◽  
Natalia Pascuali ◽  
Leopoldina Scotti ◽  
Griselda Irusta ◽  
Diana Bas ◽  
...  
Keyword(s):  
Rat Model ◽  
Ovarian Hyperstimulation Syndrome ◽  
Ovarian Hyperstimulation ◽  
Vascular Integrity ◽  
Sphingosine 1 Phosphate

Abstract 13667: Programming to S1PR1 + Endothelial Cell Population Promotes the Restoration of Vascular Integrity in vivo

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zahid Akhter ◽  
Jagdish Chandra Joshi ◽  
Vijay Avin Balaji Ragunathrao ◽  
Richard L Proia ◽  
Asrar B Malik ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Lung Injury ◽  
Endothelial Permeability ◽  
Vascular Diseases ◽  
Mechanistic Study ◽  
Rna Seq ◽  
Vascular Integrity ◽  
Injured Lung ◽  
Sphingosine 1 Phosphate

Introduction: Increased endothelial permeability and failure to repair is the hallmark of several vascular diseases including acute lung injury (ALI). However, little is known about the intrinsic pathways that activate the endothelial cell (EC) regenerative programs facilitating thereby tissue repair. Studies have invoked a crucial role of sphingosine-1-phosphate (S1P) in resolving endothelial hyperpermeability through activation of the G-protein coupled receptor, sphingosine-1-phosphate receptor 1 (S1PR1). Hypothesis: We postulate that S1PR1 + EC serve as an endogenous means to prevent endothelial injury. Methods: Studies were made using EC-S1PR1 null mice and S1PR1-GFP reporter mice to trace the generation and characteristics of S1PR1 + EC by exploiting immuno-histochemical analysis and FACS. RNA-seq analysis was performed to identify the genetic signature of S1PR1 + EC. Combination of genetic and pharmacological strategies were included for mechanistic study. Transplantation of S1PR1 + EC and edema measurement was performed in EC-S1PR1 null mice. Results: We observed in a mouse model of endotoxemia that LPS via generation of S1P induced the programming of S1PR1 lo EC to S1PR1 + EC, comprising 80% of lung EC. Their generation preceded the vascular repair phase and these cells were required for reestablishing the endothelial barrier function. Thus, conditional deletion of S1PR1 in EC spontaneously increased lung vascular permeability. RNA-seq analysis of S1PR1 + EC showed enrichment of genes regulating S1P synthesis and transport, sphingosine kinase 1 (SPHK1) and SPNS2, respectively, as well as transcription factors EGR1 and STAT3. EGR1 and STAT3 were essential for transcribing SPHK1 and SPNS2, respectively to increase S1P concentration that served to amplify S1PR1 + EC transition. Transplantation of S1PR1 + EC into injured lung vasculature of EC-S1PR1 -/- mice restored endothelial integrity. Conclusions: Findings illustrate that generation of a specialized S1PR1 + EC population has the potential to activate key endothelial regenerative program mediating vascular endothelial repair raising the possibility of activating this pathway to restore vascular homeostasis in inflammatory lung injury.

scholarly journals Platelet-derived growth factor B restores vascular barrier integrity and diminishes permeability in ovarian hyperstimulation syndrome

2020 ◽  
Vol 26 (8) ◽  
pp. 585-600
Author(s):  
Natalia Pascuali ◽  
Leopoldina Scotti ◽  
Gonzalo Oubiña ◽  
Ignacio de Zúñiga ◽  
Mariana Gomez Peña ◽  
...  
Keyword(s):  
At Risk ◽  
Growth Factor ◽  
Rat Model ◽  
Ovarian Hyperstimulation Syndrome ◽  
Regulatory Protein ◽  
Platelet Derived Growth Factor ◽  
Corpora Lutea ◽  
Ovarian Hyperstimulation ◽  
Serum Progesterone ◽  
Protein Levels

Abstract Although advances in the prediction and management of ovarian hyperstimulation syndrome (OHSS) have been introduced, complete prevention is not yet possible. Previously, we and other authors have shown that vascular endothelial growth factor, angiopoietins (ANGPTs) and sphingosine-1-phosphate are involved in OHSS etiology. In addition, we have demonstrated that ovarian protein levels of platelet-derived growth factor (PDGF) ligands -B and -D decrease in an OHSS rat model, whilst PDGFR-β and ANGPT2 remain unchanged. In the present work, we investigated the role of PDGF-B in OHSS by evaluating ligand protein levels in follicular fluid (FF) from women at risk of developing OHSS and by using an immature rat model of OHSS. We demonstrated that PDGF-B and PDGF-D are lower in FF from women at risk of developing OHSS compared to control patients (P < 0.05). In the OHSS rat model, PDGF-B (0.5 µg/ovary) administration decreased ovarian weight (P < 0.05), reduced serum progesterone (P < 0.05) and lowered the percentage of cysts (P < 0.05), compared to untreated OHSS rats, but had no effect on the proportion of follicles or corpora lutea (CL). PDGF-B treatment also restored the expression of steroidogenic acute regulatory protein (P < 0.05) and P450 cholesterol side-chain cleavage enzyme (P < 0.01) to control levels. In addition, PDGF-B increased the peri-endothelial cell area in CL and cystic structures, and reduced vascular permeability compared to untreated OHSS ovaries. Lastly, PDGF-B increased the levels of junction proteins claudin-5 (P < 0.05), occludin (P < 0.05) and β-catenin (P < 0.05), while boosting the extracellular deposition of collagen IV surrounding the ovarian vasculature (PP < 0.01), compared to OHSS alone. In conclusion, our findings indicate that PDGF-B could be another crucial mediator in the onset and development of OHSS, which may lead to the development of novel prediction markers and therapeutic strategies.

Effect of letrozole for prevention of ovarian hyperstimulation syndrome (OHSS) in a rat model

2013 ◽  
Vol 100 (3) ◽  
pp. S258 ◽  
Author(s):  
L. Akman ◽  
A. Akdogan ◽  
O. Erbas ◽  
H. Aktug ◽  
G. Sahin ◽  
...  
Keyword(s):  
Rat Model ◽  
Ovarian Hyperstimulation Syndrome ◽  
Ovarian Hyperstimulation

Targeting angiogenesis in the pathological ovary

2013 ◽  
Vol 25 (2) ◽  
pp. 362 ◽  
Author(s):  
W. Colin Duncan ◽  
Junko Nio-Kobayashi
Keyword(s):  
Ovarian Hyperstimulation Syndrome ◽  
Therapeutic Potential ◽  
Polycystic Ovary ◽  
Ovarian Hyperstimulation ◽  
Vascular Endothelial ◽  
Theoretical Possibility ◽  
Clinical Role ◽  
And Function ◽  
Endothelial Growth Factor

The ovary is a key tissue in the study of physiological neo-vascularisation in the adult and its study has highlighted important molecules involved in the regulation of angiogenesis in vivo. These include vascular endothelial growth factor, delta-like ligand 4, thrombospondin-1, prokineticin-1 and prostaglandin E2. Targeting these molecular pathways has therapeutic potential and their manipulation has an increasing preclinical and clinical role in the management of the pathological ovary. Targeting angiogenic pathways has utility in the promotion of ovarian angiogenesis to improve tissue and follicle survival and function as well as the prevention and management of ovarian hyperstimulation syndrome. There is a theoretical possibility that targeting angiogenesis may improve the function of the polycystic ovary and a real role for targeting angiogenesis in ovarian cancer.

Comparison of montelukast and cabergoline for prevention of ovarian hyperstimulation syndrome: in an experimental rat model

2015 ◽  
Vol 31 (5) ◽  
pp. 369-373 ◽  
Author(s):  
Levent Akman ◽  
Gulnaz Sahin ◽  
Oytun Erbas ◽  
Huseyin Aktug ◽  
Aysin Akdogan ◽  
...  
Keyword(s):  
Rat Model ◽  
Ovarian Hyperstimulation Syndrome ◽  
Ovarian Hyperstimulation ◽  
Experimental Rat Model

scholarly journals Ginkgo Biloba Extract 761 Reduces Vascular Permeability of the Ovary and Improves the Symptom of Ovarian Hyperstimulation Syndrome in a Rat Model

2021 ◽  
Author(s):  
Jie Zhang ◽  
Jie Huang ◽  
Xinhuan He ◽  
Ning Li ◽  
Yu Miao ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Treatment Group ◽  
Vascular Permeability ◽  
Chorionic Gonadotropin ◽  
Rat Model ◽  
Ovarian Hyperstimulation Syndrome ◽  
Ovarian Hyperstimulation ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Abstract BackgroundGinkgo biloba extract (EGb) has been widely applied in the treatment of cerebrovascular and neurological diseases. However, the effect of EGb761 on ovarian hyperstimulation syndrome (OHSS), a vascular disorder and life-threatening complication of In vitro fertilization and Intracytoplasmic sperm injection therapy (IVF/ICSI), has not been evaluated. MethodsForty female Wistar rats aged 22-days old (D22) were divided into eight groups: Control rats received intraperitoneal injection of saline for 5 consecutive days (D22-D26); OHSS-model group received 10 IU equine chorionic gonadotropin (eCG) for 4 consecutive days (D22-D25) and 30 IU of human chorionic gonadotropin (hCG) on the 5th day (D26); Prophylactic treatment group received three doses of EGb761 (50mg/kg/d, 100mg/kg/d, 200mg/kg/d) one hour before injection of eCG (hCG) for 7 consecutive days; Therapeutic treatment group received three doses of EGb761 (50mg/kg/d, 100mg/kg/d, 200mg/kg/d) 48 hours after injection of eCG (hCG) for 7 consecutive days. ResultsWe found the therapeutic treatment group exhibited the lowest ovarian and renal mass index, vascular permeability, estradiol and progesterone concentrations, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) protein expression. ConclusionsEGb761 decreases vascular permeability in OHSS rat model by inhibiting VEGF and VEGFR expression, which may contribute to the prevention and treatment of OHSS. Furthermore, therapeutic medication is superior to prophylactic medication.

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