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https://www.readbyqxmd.com/read/29860275/effects-of-glycol-split-low-molecular-weight-heparin-on-placental-endothelial-and-anti-inflammatory-pathways-relevant-to-preeclampsia
#1
Jovian M Wat, Krista Hawrylyshyn, Dora Baczyk, Iain R Greig, John C Kingdom
Low molecular weight heparin (LMWH) is being investigated as a potential preventative therapy against preeclampsia. There is evidence suggesting that LMWH may prevent preeclampsia through anticoagulation-independent mechanisms. In this study, we compared the in vitro placental, endothelial, and anti-inflammatory effects of a LMWH (dalteparin) with a non-anticoagulant, glycol-split heparin derivative (gsHep). In contrast with dalteparin, gsHep did not interact with antithrombin III, possess significant anti-Factor Xa activity, or significantly prolong in vitro plasma clotting time...
May 30, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29803833/elabela-apela-levels-are-not-decreased-in-the-maternal-circulation-or-placenta-among-women-with-preeclampsia
#2
Natasha Pritchard, Tu'uhevaha J Kaitu'u-Lino, Sungsam Gong, Justyna Dopierala, Gordon C S Smith, D Stephen Charnock-Jones, Stephen Tong
The genetic deletion of Elabela (official name APELA, encoding the peptide hormone apelin receptor early endogenous ligand) produces a preeclampsia-like phenotype in mice. However, evidence linking ELABELA with human disease is lacking. Therefore, we measured placental mRNA and circulating ELABELA in human samples. ELABELA mRNA (measured by RNA-Seq) was unchanged in 82 preeclamptic placentas compared to 82 matched controls (mean difference 0.53 %; 95% CI, -25.9 to 27.0, P = 0.78). We measured circulating ELABELA in 32 women with preterm preeclampsia (delivered <34 weeks' gestation) and 32 matched controls sampled at the same gestational age...
May 24, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29803331/angiogenic-profile-in-the-finnish-genetics-of-pre-eclampsia-consortium-finnpec-cohort
#3
Tiina Jääskeläinen, Seppo Heinonen, Esa Hämäläinen, Kari Pulkki, Jarkko Romppanen, Hannele Laivuori
OBJECTIVES: To study first and second/third trimester levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) in FINNPEC case-control cohort. The participants were further divided into subgroups based on parity and onset of the disease. Recommended cut-off values in aid of pre-eclampsia (PE) prediction and diagnosis were also tested. METHODS: First trimester serum samples were available from 221 women who later developed PE and 239 women who did not develop PE...
March 10, 2018: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29748248/bromodomain-protein-brd4-is-increased-in-human-placentas-from-women-with-early-onset-preeclampsia
#4
Stella Liong, Gillian Barker, Martha Lappas
Preeclampsia affects 5% of all pregnancies and is a serious disorder of pregnancy, characterised by high maternal blood pressure, placental hypoxia, fluid retention (oedema) and proteinuria. Women with preeclampsia are associated with exaggerated levels of pro-inflammatory cytokines, chemokines and anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFLT1). Studies in non-gestational tissues have described the bromodomain (BRD) and extraterminal family of proteins, in particular BRD4 to play a critical role in propagating inflammation and is currently a therapeutic target for treating cancer, lung inflammation and asthma...
June 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29702562/positive-and-negative-regulation-of-angiogenesis-by-soluble-vascular-endothelial-growth-factor-receptor-1
#5
REVIEW
Cristina M Failla, Miriam Carbo, Veronica Morea
Vascular endothelial growth factor receptor (VEGFR)-1 exists in different forms, derived from alternative splicing of the same gene. In addition to the transmembrane form, endothelial cells produce a soluble VEGFR-1 (sVEGFR-1) isoform, whereas non-endothelial cells produce both sVEGFR-1 and a different soluble molecule, known as soluble fms-like tyrosine kinase (sFlt)1-14. By binding members of the vascular endothelial growth factor (VEGF) family, the soluble forms reduce the amounts of VEGFs available for the interaction with their transmembrane receptors, thereby negatively regulating VEGFR-mediated signaling...
April 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29674197/villous-explants-from-preeclamptic-placentas-induce-sflt1-in-pbmcs-an-ex-vivo-co-culture-study
#6
Stephen Kyle Gonzales, Martina Badell, Hanh Cottrell, Bassam Rimawi, Venkataraman Deepak, Neil Sidell, Augustine Rajakumar
OBJECTIVES: Soluble Flt1 (sFlt1) is an anti-angiogenic protein linked to the pathology of preeclampsia (PE). While the placenta serves as the major organ producing sFlt1 during normal pregnancy, peripheral blood mononuclear cells (PBMCs), endothelial cells, and stromal cells also produce sFlt1. The key question is 'what drives the overexpression of sFlt1 observed during PE?' In the present work we show evidence for sFlt1 over-expression in PBMCs due to interaction with placental villi from PE patients...
April 2018: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29610266/causative-effects-of-genetically-determined-high-maternal-fetal-endothelin-1-on-preeclampsia-like-conditions-in-mice
#7
Feng Li, Masao Kakoki, Marcela Smid, Kim Boggess, Jennifer Wilder, Sylvia Hiller, Carol Bounajim, Scott E Parnell, Kathleen K Sulik, Oliver Smithies, Nobuyo Maeda-Smithies
Endothelin-1 (ET-1) is implicated in the pathophysiology of preeclampsia. An association between an EDN1 gene polymorphism with high ET-1 and preeclampsia was reported in humans, but their cause and effect relationships have not been defined. We examined the pregnancy effects in mice with a modified Edn1 allele that increases mRNA stability and thus ET-1 production. Heterozygous Edn1 H/ + females showed no obvious abnormalities before pregnancy, but when mated with wild-type (WT) males developed a full spectrum of preeclampsia-like phenotypes, including increased systolic blood pressure, proteinuria, glomerular endotheliosis, and intrauterine fetal growth restriction...
May 2018: Hypertension
https://www.readbyqxmd.com/read/29523283/the-role-of-angiogenic-biomarkers-and-uterine-artery-doppler-in-pregnant-women-with-systemic-lupus-erythematosus-or-antiphospholipid-syndrome
#8
M E Rodríguez-Almaraz, I Herraiz, P I Gómez-Arriaga, P Vallejo, E Gonzalo-Gil, A Usategui, E A López-Jiménez, A Galindo, M Galindo
OBJECTIVE: To evaluate the usefulness of the uterine artery mean pulsatility index (mPI-UtA) and the sFlt-1/PlGF ratio in women with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS) for the prediction of placental dysfunction-related adverse outcomes (AO), namely pre-eclampsia (PE) and intrauterine growth restriction (IUGR), and for differential diagnosis between PE and SLE flares. STUDY DESIGN: Observational prospective cohort study of 57 pregnant women with SLE or APS...
January 2018: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29523276/analytical-validation-of-soluble-fms-like-tyrosine-and-placental-growth-factor-assays-on-b%C3%A2-r%C3%A2-a%C3%A2-h%C3%A2-m%C3%A2-s-kryptor-compact-plus-automated-immunoassay-platform
#9
Siaw Li Chan, Sarosh Rana, Sireesha Chinthala, Saira Salahuddin, Kiang-Teck J Yeo
BACKGROUND: Preeclampsia is one of the leading hypertensive disorders of pregnancy. Angiogenic biomarkers such as anti-angiogenic factor soluble fms-like tyrosine kinase 1 (sFlt1) and pro-angiogenic factor placental growth factor (PlGF) are involved in the pathophysiology of preeclampsia. OBJECTIVE: The aim of this study is to validate the analytical performance of sFlt1 and PlGF on the B·R·A·H·M·S KRYPTOR Compact Plus (ThermoFisher Scientific). STUDY DESIGN: We examined K2 -EDTA plasma samples from 50 patients on B·R·A·H·M·S KRYPTOR Compact Plus, an automated immunoassay platform...
January 2018: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29523274/an-sflt-1-plgf-ratio-of-655-is-not-a-reliable-cut-off-value-for-predicting-perinatal-outcomes-in-women-with-preeclampsia
#10
Myriam Stolz, Harald Zeisler, Florian Heinzl, Julia Binder, Alex Farr
OBJECTIVES: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is increased in preeclampsia. This study evaluated perinatal outcomes in cases with an sFlt-1:PlGF ratio above 655. STUDY DESIGN: We retrospectively analyzed data from all consecutive women with singleton pregnancies who presented with clinically manifest preeclampsia and underwent immediate sFlt-1:PlGF assessment. Cases with an sFlt-1:PlGF ratio ≥ 655 were matched 1:1 for gestational age to controls with a ratio < 655...
January 2018: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29473285/angiogenic-factors-in-pre-eclampsia-implications-for-clinical-practice
#11
S A Karumanchi
No abstract text is available yet for this article.
February 23, 2018: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/29437897/tlr9-toll-like-receptor-9-agonist-suppresses-angiogenesis-by-differentially-regulating-vegfa-vascular-endothelial-growth-factor-a-and-sflt1-soluble-vascular-endothelial-growth-factor-receptor-1-in-preeclampsia
#12
Biwei He, Xingyu Yang, Yamei Li, Ding Huang, Xin Xu, Wenjun Yang, Yan Dai, Huijuan Zhang, Zhengjun Chen, Weiwei Cheng
Preeclampsia is a common pregnancy-specific disorder characterized by elevated blood pressure and proteinuria. Activation of the maternal immune system and impaired placental angiogenesis are thought to contribute to the pathogenesis of preeclampsia. TLR9 (Toll-like receptor 9) plays a role in innate immunity, defending the organism against infection. The purpose of this study was to determine whether TLR9 inhibits angiogenesis at the fetomaternal interface under conditions of preeclampsia. We confirmed the downregulation of VEGFA (vascular endothelial growth factor A) and upregulation of TLR9 and sFLT1 (soluble vascular endothelial growth factor receptor 1) in placentas from preeclamptic women...
April 2018: Hypertension
https://www.readbyqxmd.com/read/29311569/hepatic-dysfunction-and-thrombocytopenia-induced-by-excess-sflt1-in-mice-lacking-endothelial-nitric-oxide-synthase
#13
Yuji Oe, Mieko Ko, Tomofumi Fushima, Emiko Sato, S Ananth Karumanchi, Hiroshi Sato, Junichi Sugawara, Sadayoshi Ito, Nobuyuki Takahashi
Liver dysfunction is a major problem in patients with severe preeclampsia (PE), hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, or in patients receiving anti-vascular endothelial growth factor (VEGF) therapy. Excessive soluble fms-like tyrosine kinase 1 (sFlt1) that antagonizes VEGF has been implicated in the pathogenesis of PE. VEGF increases the expression of endothelial nitric oxide synthase (eNOS) and activates it. eNOS polymorphisms that cause reduced NO production are associated with PE...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29208243/resveratrol-mitigates-trophoblast-and-endothelial-dysfunction-partly-via-activation-of-nuclear-factor-erythroid-2-related-factor-2
#14
Seshini Gurusinghe, Annie G Cox, Rahana Rahman, Siow T Chan, Ruth Muljadi, Harmeet Singh, Bryan Leaw, Joanne C Mockler, Sarah A Marshall, Padma Murthi, Rebecca Lim, Euan M Wallace
INTRODUCTION: Maternal endothelial dysfunction underlying preeclampsia arises from excessive placental release of anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and activin A. Resveratrol, an activator of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, mediates the gene expression of antioxidant and vasoprotective factors that may counter the endothelial damage imposed by these anti-angiogenic factors. The objective of this study was to assess whether resveratrol could reduce placental oxidative stress and production of anti-angiogenic factors in vitro and/or improve in vitro markers of endothelial dysfunction via Nrf2 activation...
December 2017: Placenta
https://www.readbyqxmd.com/read/29196991/biomarker-immunoassays-in-the-diagnosis-of-preeclampsia-calculating-the-sflt1-plgf-ratio-using-the-cobas-%C3%A2-e-411-analyser
#15
Carin Black, Fabricio da Silva Costa
Preeclampsia is a relatively common pregnancy-related condition associated with serious maternal and fetal morbidity and mortality. It is now well established that anti-angiogenic sFlt1 is upregulated in preeclampsia and binds PlGF and VEGF, causing an imbalance in angiogenic factors with subsequent endothelial injury and dysfunction. Measurement of placental growth factor (PlGF) and the sFlt1/PlGF ratio have both been validated in other countries for screening and diagnosis of preeclampsia and the differentiation of preeclampsia from other hypertensive disorders of pregnancy...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29168351/complement-5a-mediated-trophoblasts-dysfunction-is-involved-in-the-development-of-pre-eclampsia
#16
Yu Ma, Ling-Ran Kong, Qian Ge, Yuan-Yuan Lu, Mo-Na Hong, Yu Zhang, Cheng-Chao Ruan, Ping-Jin Gao
Pre-eclampsia (PE) is a life-threatening multisystem disorder leading to maternal and neonatal mortality and morbidity. Emerging evidence showed that activation of the complement system is implicated in the pathological processes of PE. However, little is known about the detailed cellular and molecular mechanism of complement activation in the development of PE. In this study, we reported that complement 5a (C5a) plays a pivotal role in aberrant placentation, which is essential for the onset of PE. We detected an elevated C5a deposition in macrophages and C5a receptor (C5aR) expression in trophoblasts of pre-eclamptic placentas...
February 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29153696/dysregulation-of-circulating-autoantibodies-against-vegf-a-vegfr-1-and-plgf-in-preeclampsia-a-role-in-placental-and-vascular-health
#17
Kjartan Moe, Harald Heidecke, Ralf Dechend, Anne Cathrine Staff
OBJECTIVES: Preeclampsia is a state of antiangiogenesis, with high levels of maternal circulating sVEGFR-1 (soluble vascular endothelial growth factor receptor 1, also named sFlt1) and low levels of PlGF (placenta growth factor). Various autoantibodies have been detected in preeclamptic patients. We hypothesize that circulating autoantibodies against VEGF-A (AA-VEGF-A), VEGFR-1 (AA-VEGFR-1) and PlGF (AA-PlGF) are present in preeclamptic women, with different levels from pregnant women with normotensive pregnancies...
October 2017: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29138037/genetic-predisposition-to-preeclampsia-is-conferred-by-fetal-dna-variants-near-flt1-a-gene-involved-in-the-regulation-of-angiogenesis
#18
Kathryn J Gray, Richa Saxena, S Ananth Karumanchi
Preeclampsia risk is influenced by both the mother's genetic background and the genetics of her fetus; however, the specific genes responsible for conferring preeclampsia risk have largely remained elusive. Evidence that preeclampsia has a genetic predisposition was first detailed in the early 1960s, and overall preeclampsia heritability is estimated at ∼55%. Many traditional gene discovery approaches have been used to investigate the specific genes that contribute to preeclampsia risk, but these have largely not been successful or reproducible...
February 2018: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28967436/the-angiogenic-properties-of-human-adipose-derived-stem-cells-hascs-are-modulated-by-the-high-mobility-group-box-protein-1-hmgb1
#19
Federico Biscetti, Stefano Gentileschi, Flavio Bertucci, Maria Servillo, Vincenzo Arena, Flavia Angelini, Egidio Stigliano, Giuseppina Bonanno, Giovanni Scambia, Benedetto Sacchetti, Luca Pierelli, Raffaele Landolfi, Andrea Flex
Peripheral arterial disease (PAD), is a major health problem. Many studies have been focused on the possibilities of treatment offered by vascular regeneration. Human adipose-derived stem cells (HASCs), multipotent CD34+ stem cells found in the stromal-vascular fraction of adipose tissues, which are capable to differentiate into multiple mesenchymal cell types. The High mobility group box 1 protein (HMGB1) is a nuclear protein involved in angiogenesis. The aim of the study was to define the role of HMGB1 in cell therapy with HASCs, in an animal model of PAD...
December 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28962687/modulating-circulating-sflt1-in-an-animal-model-of-preeclampsia-using-pamam-nanoparticles-for-sirna-delivery
#20
Jun Yu, Jing Jia, Xijiao Guo, Ruibao Chen, Ling Feng
INTRODUCTION: Excessive circulating sFlt1 plays a major role in the pathogenesis of preeclampsia (PE). Using RNAi to silence sFlt1 may be a therapy for treating PE. Because of the rapid degradation of siRNA, gene therapy in vivo remains limited. Poly-amidoamine (PAMAM) has been demonstrated to be an excellent nanocarrier for siRNA delivery with no discernible toxicity. METHODS: The aim of the present study was to investigate the therapeutic effect of siRNA-sFlt1-PAMAM on PE...
October 2017: Placenta
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