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https://www.readbyqxmd.com/read/29674197/villous-explants-from-preeclamptic-placentas-induce-sflt1-in-pbmcs-an-ex-vivo-co-culture-study
#1
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...
February 25, 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
#2
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...
April 2, 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
#3
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
#4
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
#5
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
#6
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
#7
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...
February 5, 2018: Hypertension
https://www.readbyqxmd.com/read/29311569/hepatic-dysfunction-and-thrombocytopenia-induced-by-excess-sflt1-in-mice-lacking-endothelial-nitric-oxide-synthase
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28949775/evaluation-of-sflt1-protein-levels-in-human-eyes-with-the-flt1-rs9943922-polymorphism
#16
Kathleen R Chirco, Carly J Lewis, Todd E Scheetz, Rebecca M Johnston, Budd A Tucker, Edwin M Stone, John H Fingert, Robert F Mullins
PURPOSE: Age-related macular degeneration (AMD) is a devastating disease characterized by central vision impairment in individuals with advanced age. Neovascular AMD is a form of end-stage disease in which choroidal vessel outgrowth occurs beneath the retina. While many hypotheses have been raised as to what triggers the formation of pathological choroidal neovascular membranes, the exact mechanism for their initiation remains unresolved. Polymorphisms in the FLT1 gene have previously been associated with neovascular AMD risk, including the rs9943922 single nucleotide polymorphism (SNP)...
January 2018: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28939895/a-single-sphingomyelin-species-promotes-exosomal-release-of-endoglin-into-the-maternal-circulation-in-preeclampsia
#17
Leonardo Ermini, Jonathan Ausman, Megan Melland-Smith, Behzad Yeganeh, Alessandro Rolfo, Michael L Litvack, Tullia Todros, Michelle Letarte, Martin Post, Isabella Caniggia
Preeclampsia (PE), an hypertensive disorder of pregnancy, exhibits increased circulating levels of a short form of the auxillary TGF-beta (TGFB) receptor endoglin (sENG). Until now, its release and functionality in PE remains poorly understood. Here we show that ENG selectively interacts with sphingomyelin(SM)-18:0 which promotes its clustering with metalloproteinase 14 (MMP14) in SM-18:0 enriched lipid rafts of the apical syncytial membranes from PE placenta where ENG is cleaved by MMP14 into sENG. The SM-18:0 enriched lipid rafts also contain type 1 and 2 TGFB receptors (TGFBR1 and TGFBR2), but not soluble fms-like tyrosine kinase 1 (sFLT1), another protein secreted in excess in the circulation of women with PE...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28939845/flt1-and-transcriptome-wide-polyadenylation-site-pas-analysis-in-preeclampsia
#18
Ami Ashar-Patel, Yasin Kaymaz, Augustine Rajakumar, Jeffrey A Bailey, S Ananth Karumanchi, Melissa J Moore
Maternal symptoms of preeclampsia (PE) are primarily driven by excess anti-angiogenic factors originating from the placenta. Chief among these are soluble Flt1 proteins (sFlt1s) produced from alternatively polyadenylated mRNA isoforms. Here we used polyadenylation site sequencing (PAS-Seq) of RNA from normal and PE human placentae to interrogate transcriptome-wide gene expression and alternative polyadenylation signatures associated with early-onset PE (EO-PE; symptom onset < 34 weeks) and late-onset PE (LO-PE; symptom onset > 34 weeks) cohorts...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889770/angiogenic-factors-for-prediction-of-preeclampsia-and-intrauterine-growth-restriction-onset-in-high-risk-women-angiopred-study
#19
Tiphaine Raia-Barjat, Carole Prieux, Jean-Christophe Gris, Céline Chapelle, Silvy Laporte, Céline Chauleur
OBJECTIVE: The study aimed to compare the level of two angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), for the prediction of preeclampsia and intrauterine growth restriction in high-risk pregnant women. METHODS: A prospective multicenter cohort study of 200 pregnant patients was conducted between June 2008 and October 2010. sFlt1 and sEng were measured by enzyme-linked immunosorbent assay. RESULTS: Forty-five patients developed a placenta-mediated adverse pregnancy outcome...
September 22, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28876491/longitudinal-changing-values-of-the-sflt-1-plgf-ratio-in-singleton-pregnancies-with-early-onset-fetal-growth-restriction
#20
I Herraiz, M S Quezada, J Rodriguez-Calvo, E Gómez-Montes, C Villalaín, A Galindo
OBJECTIVE: To describe, in singleton pregnancies complicated with early-onset fetal growth restriction (FGR), the progressing values of the sFlt-1/PlGF ratio in the weeks prior to delivery, differentiating cases with and without pre-eclampsia (PE). METHODS: Prospective cohort observational study of early-onset FGR cases followed with maternal serum determinations of the sFlt-1/PlGF ratio from diagnosis to delivery. Measurements were made at weekly intervals and within the last 48 hours before birth...
September 6, 2017: Ultrasound in Obstetrics & Gynecology
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