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placental angiogenic factors

Yinghong Zhang, Xianzhen Pan, Xiaoyan Yu, Lei Li, Hongmei Qu, Shuhong Li
BACKGROUND: The remodeling of maternal spiral artery following embryo implantation, which relies on well-regulated trophoblast functions, is a pivotal process to ensure a successful pregnancy. Low-density lipoprotein receptor-related protein 6 (LRP6) and microRNAs (miRNAs, miRs) are suggested to be involved in angiogenesis and several vascular diseases; however, their functions in the control of trophoblast remain elusive. We therefore aimed to examine the roles of LRP6 and miR-590-3p in the regulation of trophoblast during the remodeling of maternal spiral artery...
November 8, 2018: Molecular Genetics & Genomic Medicine
Marta Ribeiro Hentschke, Edson Vieira da Cunha Filho, Matias Costa Vieira, Letícia Germany Paula, Hiten D Mistry, Bartira Ercília Pinheiro da Costa, Carlos Eduardo Poli-de-Figueiredo
OBJECTIVE:  To analyze endocan-1, a biomarker of vascular endothelial related pathologies, and the placental growth factor (PlGF), an angiogenic factor and a placental dysfunction marker in patients with preeclampsia (PE). METHODS:  Case-control study conducted at Hospital São Lucas, in the city of Porto Alegre, Brazil. Endocan-1 and PlGF levels were quantified in the maternal plasma using the MagPlexTH-C microsphere system (MAGPIX System, Luminex, Austin, Texas, US) and evaluated through analysis of covariance (ANCOVA) and adjusted by body mass index (BMI), gestational age and maternal age...
October 2018: Revista Brasileira de Ginecologia e Obstetrícia
Sanjay Basak, Vilasagaram Srinivas, Asim K Duttaroy
Humans are exposed to Bisphenol A (BPA) from the consumer products and plastic substances. However, impacts of low levels of BPA exposure on placental developmental processes such as first trimester trophoblast cell growth, angiogenesis and epigenetic modifications are not well studied. Low concentration of BPA (1 nM) affected cell proliferation of human placental first trimester trophoblasts using a model cell, HTR8/SVneo. BPA abolished both basal- and vascular endothelial growth factor (VEGF)-stimulated tube formation in these cells...
October 21, 2018: Reproductive Toxicology
Wentao Yu, Wei Gao, Dan Rong, Zhixian Wu, Raouf A Khalil
Preeclampsia is a pregnancy-related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia and reduced uterine perfusion pressure (RUPP). RUPP causes imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, and stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies...
October 19, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Regina A Nascimento, José S Possomato-Vieira, Victor H Gonçalves-Rizzi, Gisele F Bonacio, Elen Rizzi, Carlos A Dias-Junior
Preeclampsia is manifested as maternal hypertension and fetal growth restriction. Matrix metalloproteinases (MMPs) are involved in hypertension and doxycycline reduces blood pressure by inhibition of MMPs. Moreover, excessive levels of MMPs and reduced nitric oxide (NO) bioavailability have been related to preeclampsia. We investigated the involvement of MMPs in hypertension in pregnancy induced by Nω-Nitro-L-arginine methyl ester (L-NAME) in rats. To this end, zimography was performed to evaluate the activity of MMPs -2 and -9 in placenta, uterus and thoracic aorta, and systolic blood pressure, feto-placental development and metabolites of NO were evaluated...
December 5, 2018: European Journal of Pharmacology
Jessica Sabbatine Chimini, Jose Sergio Possomato-Vieira, Maria Luiza Santos da Silva, Carlos A Dias-Junior
preeclampsia and hypertensive disorders of pregnancy are frequently associated with feto-placental growth restriction and that may be triggered by angiogenic imbalance and endothelial dysfunction. Impaired nitric oxide (NO) bioavailability seems to be involved in these pathophysiological changes observed in hypertensive pregnancy. Pravastatin has shown efficacy and to be safe during hypertension in pregnancy. However, NO involvement in pravastatin effects during maternal hypertension and feto-placental development is unclear...
October 14, 2018: Basic & Clinical Pharmacology & Toxicology
Ambart E Covarrubias, Edouard Lecarpentier, Agnes Lo, Saira Salahuddin, Kathryn J Gray, S Ananth Karumanchi, Zsuzsanna K Zsengellér
Although the etiology of preeclampsia, a pregnancy complication with significant maternal and neonatal morbidity, has not been fully characterized, placental ischemia due to impaired spiral artery remodeling and abnormal secretion of anti-angiogenic factors are thought to be important in the pathogenesis of the disease. Placental ischemia could impair trophoblast mitochondrial function and energy production leading to the release of reactive oxygen species (ROS). ROS has been shown to stabilize hypoxia inducible factor (HIF-1α), which in turn may induce transcription of anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin in trophoblasts...
October 10, 2018: American Journal of Pathology
Jana Kleiner, Margrit Hollborn, Peter Wiedemann, Andreas Bringmann
Purpose: Systemic hypertension is a risk factor of neovascular age-related macular degeneration; consumption of dietary salt resulting in extracellular hyperosmolarity is a main cause of hypertension. Extracellular hyperosmolarity was shown to induce expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), in RPE cells. The aim of the present study was to determine whether the hyperosmotic expression of growth factor genes in RPE cells is mediated by activator protein-1 (AP-1), and whether c-Fos and c-Jun genes are regulated by extracellular osmolarity...
2018: Molecular Vision
Yan Li, Gladys E Lopez, Jessica Vazquez, Yan Sun, Melina Chavarria, Payton N Lindner, Samantha Fredrickson, Nathan Karst, Aleksandar K Stanic
Adaptive immune system, principally governed by the T cells-dendritic cells (DCs) nexus, is an essential mediator of gestational fetal tolerance and protection against infection. However, the exact composition and dynamics of DCs and T cell subsets in gestational tissues are not well understood. These are controlled in human physiology by a complex interplay of alloantigen distribution and presentation, cellular/humoral active and passive tolerance, hormones/chemokines/angiogenic factors and their gradients, systemic and local microbial communities...
2018: Frontiers in Immunology
Kristina Kumer, Tanja Premru-Sršen, Vesna Fabjan-Vodušek, Nataša Tul, Teja Fabjan, Joško Osredkar
OBJECTIVE: To evaluate changes in vascular function and serum biomarkers in women with and without preeclampsia (PE) to create a model for the easier and more precise diagnosis of PE in the future. METHODS: Endothelial function and arterial stiffness were evaluated using peripheral arterial tonometry and concentrations of placental growth factor (PlGF), soluble fms like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were determined by immunoassay. RESULTS: Arterial stiffness deteriorates and endothelial function is better in women with PE compared with a healthy pregnancy...
October 4, 2018: Hypertension in Pregnancy
Ramin Khanabdali, Aida Shakouri-Motlagh, Sarah Wilkinson, Padma Murthi, Harry M Georgiou, Shaun P Brennecke, Bill Kalionis
Preeclampsia (PE) is a hypertensive disorder of human pregnancy. Low-dose aspirin (acetylsalicylic acid) (60-150 mg/day) is used to prevent PE when taken early in pregnancy. The effect of aspirin on term PE remains uncertain. Abnormal placentation is a hallmark of PE and leads to increased placental oxidative stress, which triggers the release of anti-angiogenic factors that cause local damage to the decidual vasculature. The damage subsequently spreads systemically and culminates in maternal clinical symptoms...
November 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Weronika Dymara-Konopka, Marzena Laskowska, Anna Blazewicz
Preeclampsia is one of the most serious pregnancy - specific medical conditions affecting 3-6% of all gestations. It remains a leading cause of maternal and fetal morbidity and mortality. The aetiology of preeclampsia is not fully elucidated yet, although a huge progress has been made in its understanding within the last decade. Numerous studies have provided compelling evidence that an excess of some antiangiogenic molecules released by the placenta to maternal circulation, in particular soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) and decreased levels of proangiogenic substances like placental growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) play a key role in the pathogenesis of preeclampsia...
September 25, 2018: Current Pharmaceutical Biotechnology
Weronika Dymara-Konopka, Marzena Laskowska, Jan Oleszczuk
Preeclampsia is one of the most serious pregnancy - specific medical conditions of increasing incidence. It remains a major cause of maternal and fetal morbidity and mortality. Although maternal mortality is especially high in developing countries, preeclampsia and its complications are one of the top four causes of maternal deaths even in developed societies. Unfortunately, yet the only effective and definitive treatment of preeclampsia is delivery of the baby and placenta, and its time depends on the disease severity and gestational age...
September 25, 2018: Current Pharmaceutical Biotechnology
Tiina Jääskeläinen, Seppo Heinonen, Esa Hämäläinen, Kari Pulkki, Jarkko Romppanen, Hannele Laivuori
BACKGROUND: While several studies have demonstrated that obesity increases the risk of pre-eclampsia (PE), the mechanisms have yet to be elucidated. We assessed the association between maternal/paternal obesity and PE and hypothesized that maternal body mass index (BMI) would be associated with an adverse inflammatory and angiogenic profile. High-sensitivity C-reactive protein (hs-CRP) and following serum angiogenic markers were determined: soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF)...
September 25, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Jing Zhou, Nan-Nan Wu, Rui-Li Yin, Wei Ma, Cen Yan, Ying-Mei Feng, Chuan-Hai Zhang, Dong Zhao
Gestational diabetes mellitus (GDM) is a type of diabetes and occurs during pregnancy. Brown adipose tissue (BAT) improves glucose homeostasis and mitigates insulin resistance, however, its activity is reduced in GDM. Placenta growth factor (PlGF) is an angiogenic factor produced by placental trophoblasts. Nevertheless, whether and how PlGF could affect BAT function in GDM are not defined. To investigate this question, 91 non-diabetic pregnant participants and 73 GDM patients were recruited to Gynaecology and Obstetrics Centre in Lu He hospital...
October 2, 2018: Biochemical and Biophysical Research Communications
Jacqueline G Parchem, Keizo Kanasaki, Megumi Kanasaki, Hikaru Sugimoto, Liang Xie, Yuki Hamano, Soo Bong Lee, Vincent H Gattone, Samuel Parry, Jerome F Strauss, Vesna D Garovic, Thomas F McElrath, Karen H Lu, Baha M Sibai, Valerie S LeBleu, Peter Carmeliet, Raghu Kalluri
Preeclampsia remains a clinical challenge due to its poorly understood pathogenesis. A prevailing notion is that increased placental production of soluble fms-like tyrosine kinase-1 (sFlt-1) causes the maternal syndrome by inhibiting proangiogenic placental growth factor (PlGF) and VEGF. However, the significance of PlGF suppression in preeclampsia is uncertain. To test whether preeclampsia results from the imbalance of angiogenic factors reflected by an abnormal sFlt-1/PlGF ratio, we studied PlGF KO (Pgf-/-) mice and noted that the mice did not develop signs or sequelae of preeclampsia despite a marked elevation in circulating sFLT-1...
November 1, 2018: Journal of Clinical Investigation
Do-Hyun Kim, Seung Han Shin, Ee-Kyung Kim, Han-Suk Kim
OBJECTIVES: To investigate whether the levels of angiogenic factors in cord blood are associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants with maternal preeclampsia. STUDY DESIGN: This retrospective cohort study included 199 singleton infants (gestational age < 32 weeks), including the preeclampsia group (59 infants) with severe/moderate BPD (24 infants) or no/mild BPD (35 infants) and the no preeclampsia group (140 infants)...
July 2018: Pregnancy Hypertension
Sarosh Rana, Saira Salahuddin, Ariel Mueller, Anders H Berg, Ravi I Thadhani, S Ananth Karumanchi
There is an urgent need for biomarkers that can help stratify women with suspected preeclampsia (PE) for the subsequent appearance of PE with severe features (sPE), to improve risk assessment and direct monitoring related to complications of sPE. Elevated levels of circulating anti-angiogenic factors like soluble fms-like tyrosine kinase 1 (sFlt1) and decreased free levels of pro-angiogenic factors such as placental growth factor (PlGF) are associated with adverse outcomes related to preeclampsia (PE). Here, we report in a single-center prospective study (N = 402) that plasma levels of these circulating angiogenic markers predict sPE within two weeks among women presenting with suspected PE in the preterm period (<37 weeks)...
July 2018: Pregnancy Hypertension
Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Ping Cannon, Vi Nguyen, Tu'uhevaha J Kaitu'u-Lino
OBJECTIVES: To examine the effect of sildenafil on level of antiangiogenic proteins of preeclampsia. Firstly to examine the effect of sildenafil on serum biomarkers in a patient with preterm preeclampsia. Secondly, to examine the effect of sildenafil on sFlt-1 and soluble endoglin secretion from primary trophoblasts and placental explants. STUDY DESIGN: The clinical team administered 50 mg tds sildenafil to a 26-year-old primigravid woman with severe preeclampsia at the threshold of viability (24 3/7 weeks gestation) and we collected bloods to examine the effect of slidenafil on antiangiogenic factors sFlt-1 and soluble endoglin (sENG), pro-angiogenic factor PlGF and vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET1)...
July 2018: Pregnancy Hypertension
Lena Heidi Bækgaard Thorsen, Louise Bjørkholt Andersen, Anna Birukov, Sine Lykkedegn, Ralf Dechend, Jan Stener Jørgensen, Henrik Thybo Christesen
PURPOSE: To investigate the predictive performance of placental growth factor (PlGF) and soluble FMS-like kinase 1 (sFlt-1) on birth weight and small for gestational age (SGA), in a large, population-based cohort. METHODS: Women enrolled in the population-based, prospective Odense Child Cohort Study with early (GA < 20 weeks) and/or late (≥20 weeks) pregnancy blood samples (n = 1937) were included. The association between log-transformed values of the biomarkers and birth weight Z-score was studied using multivariate regression models...
September 25, 2018: Journal of Maternal-fetal & Neonatal Medicine
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