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Amy M Gratton, Louie Ye, Fiona C Brownfoot, Natalie J Hannan, Clare Whitehead, Ping Cannon, Minh Deo, Peter J Fuller, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino
INTRODUCTION: Preeclampsia is a serious complication of pregnancy affecting 5% of pregnancies. Our team identified 137 genes highly expressed in placenta relative to other human tissues. Here, we have explored a role for steroid sulfatase (STS) in preeclampsia by characterising STS expression and the functional effects of STS on primary placental trophoblasts. METHODS: Characterisation of STS was performed on preterm preeclamptic and gestation-matched normotensive preterm controls who delivered at <34 weeks gestation...
December 2016: Placenta
Oliver A Stone, James G Carter, P Charles Lin, Ewa Paleolog, Maria J C Machado, David O Bates
Signalling through VEGF receptors and the Tie2 receptor by angiopoietins is required in combination with blood flow for the formation of a functional vascular network. We tested the hypothesis that VEGF and Ang1 contribute differentially to neovascularization induced by nitric oxide (NO) mediated vasodilatation, by comparing the phenotype of new microvessels in the mesentery during induction of vascular remodelling by over-expression of endothelial nitric oxide synthase (eNOS) in the fat pad of the adult rat mesentery during inhibition of Angiopoietin signalling with soluble Tie2 and VEGF signalling with sFlt1...
November 21, 2016: Journal of Physiology
Ryota L Matsuoka, Michele Marass, Avdesh Avdesh, Christian Sm Helker, Hans-Martin Maischein, Ann S Grosse, Harmandeep Kaur, Nathan D Lawson, Wiebke Herzog, Didier Yr Stainier
Vascular networks surrounding individual organs are important for their development, maintenance, and function; however, how these networks are assembled remains poorly understood. Here we show that CNS progenitors, referred to as radial glia, modulate vascular patterning around the spinal cord by acting as negative regulators. We found that radial glia ablation in zebrafish embryos leads to excessive sprouting of the trunk vessels around the spinal cord, and exclusively those of venous identity. Mechanistically, we determined that radial glia control this process via the Vegf decoy receptor sFlt1: sflt1 mutants exhibit the venous over-sprouting observed in radial glia-ablated larvae, and sFlt1 overexpression rescues it...
November 17, 2016: ELife
Martina Montagnana, Elisa Danese, Giuseppe Lippi, Cristiano Fava
Preeclampsia (PE) affects 2-8% of pregnancies worldwide, thus representing an important cause of maternal and neonatal morbidity, up to death. Many studies have been designed to identify putative biomarkers for accurate and timely diagnosing PE, but only some of them were focused on specific and sensitive biomarkers for early prediction of this life-threatening condition. In particular, some prospective studies aimed to investigate the predictive role of circulating biomarkers before 20 weeks of gestation in the general pregnant population yielded conflicting results...
October 28, 2016: Annals of Medicine
Juneo F Silva, Natália M Ocarino, Rogéria Serakides
The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated...
October 14, 2016: Reproduction, Fertility, and Development
Sarah M Isaac, Dawei Qu, S Lee Adamson
INTRODUCTION: Placental examination is recommended when genetic mutations cause fetal lethality in mice. But how fetal death alters histomorphology of the surviving mouse placenta is not known. METHODS: Placentas were examined at E17.5 after fetectomy of 1-2 fetal mice per pregnancy at either embryonic day (E) 15.5 (N = 8; Fx-2 group) or E13.5 (N = 5; Fx-4 group), which left 12 ± 2 surviving fetuses per litter. RESULTS: Fetectomy caused no changes in placental weights and no increases in placental hypoxia (pimonidazole staining)...
October 2016: Placenta
Numan Cim, Mertihan Kurdoglu, Serhat Ege, Ibrahim Yoruk, Gorkem Yaman, Recep Yildizhan
AIM: The aim of this study was to evaluate the roles of proangiogenic factors including serum vitamin D and vascular endothelial growth factor (VEGF) and anti-angiogenic factors including soluble endoglin (sEng) and soluble fms-like tyrosine kinase 1 (sFlt1) in the diagnosis and severity of late-onset preeclampsia. MATERIALS AND METHODS: The study was conducted at Yuzuncu Yil University Research and Education Hospital Department of Gynecology and Obstetrics. The study included a patient group of 40 women with late-onset preeclampsia who were pregnant at ≥32 weeks of gestation according to the last menstrual period (LMP) or ultrasonographic fetal biometric measurement and a control group of 40 healthy pregnant women who presented to our clinic for routine pregnancy examination and were at the same age and gestational period with those in the patient group...
September 23, 2016: Journal of Maternal-fetal & Neonatal Medicine
Ramanathan K Kasimanickam
The objective was to elucidate gene expression differences in uterus, caruncle, and cotyledon of ewes with subclinical pregnancy toxemia (SCPT) and healthy ewes, and to identify associated biological functions and pathways involved in pregnancy toxemia. On Day 136 (±1 day) post-breeding, ewes (n = 18) had body condition score (BCS; 1-5; 1, emaciated; 5, obese) assessed, and blood samples were collected for plasma glucose and β-hydroxybutyrate (BHBA) analyses. The ewes were euthanized, and tissue samples were collected from the gravid uterus and placentomes...
2016: Frontiers in Veterinary Science
Y Ma, C Ruan, L Kong, Y Zhang, P Gao
OBJECTIVE: Increasing evidence suggests that complement activation plays a vital role in the pathogenesis of preeclampsia (PE). However, little is known about the detailed cellular and molecular mechanism of complement activation in the development of PE. Here we investigate that whether macrophage-derived complement C5a contributes to the pathophysiology of PE through its effect on trophoblasts. DESIGN AND METHOD: A total of 55 women (32 healthy pregnant women and 23 women with PE) were recruited...
September 2016: Journal of Hypertension
Allen Meeme, Geoffrey A Buga, MaryKutty Mammen, Ambrose V Namugowa
OBJECTIVE: The pathogenesis of preeclampsia remains unclear despite extensive research. Altered angiogenic balance has been hypothesized to play a significant role in the clinical manifestations of this syndrome. However this imbalance has not been investigated extensively among black African women. The aim of this study was to investigate the maternal levels of the angiogenic factors soluble vascular endothelial growth factor receptor 1 (sFLT1) and placental growth factor (PlGF) among black African women with preeclampsia...
August 8, 2016: Journal of Maternal-fetal & Neonatal Medicine
Theresa Vilsmaier, Brigitte Rack, Wolfgang Janni, Udo Jeschke, Tobias Weissenbacher
BACKGROUND: Circulating tumour cells (CTCs) have been found to be a prognostic marker for reduced disease free survival, breast cancer-specific survival, and overall survival before the start of systemic treatment. METHODS: A total of 200 patients' sera were included in this study, 100 patients being CTC positive and 100 patients being CTC negative. Matching criteria were histo-pathological grading, lymph node metastasis, hormone receptor status, TNM classification and survived breast cancer patients vs...
2016: BMC Cancer
Andrea Aguilar
No abstract text is available yet for this article.
August 2016: Nature Reviews. Nephrology
Suzanne D Burke, Zsuzsanna K Zsengellér, Eliyahu V Khankin, Agnes S Lo, Augustine Rajakumar, Jennifer J DuPont, Amy McCurley, Mary E Moss, Dongsheng Zhang, Christopher D Clark, Alice Wang, Ellen W Seely, Peter M Kang, Isaac E Stillman, Iris Z Jaffe, S Ananth Karumanchi
Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and is associated with substantial morbidity for the mother and fetus. Enhanced vasoconstrictor sensitivity and elevations in soluble fms-like tyrosine kinase 1 (sFLT1), a circulating antiangiogenic protein, precede clinical signs and symptoms of preeclampsia. Here, we report that overexpression of sFlt1 in pregnant mice induced angiotensin II sensitivity and hypertension by impairing endothelial nitric oxide synthase (eNOS) phosphorylation and promoting oxidative stress in the vasculature...
July 1, 2016: Journal of Clinical Investigation
Tansim Akhter, Anna-Karin Wikström, Marita Larsson, Anders Larsson, Gerhard Wikström, Tord Naessen
OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE...
June 3, 2016: Ultrasound in Obstetrics & Gynecology
Lukasz Przybyl, Nadine Haase, Michaela Golic, Julianna Rugor, Maria Emilia Solano, Petra Clara Arck, Martin Gauster, Berthold Huppertz, Christoph Emontzpohl, Christian Stoppe, Jürgen Bernhagen, Lin Leng, Richard Bucala, Herbert Schulz, Arnd Heuser, M Susanne Weedon-Fekjær, Guro M Johnsen, Dirk Peetz, Friedrich C Luft, Anne Cathrine Staff, Dominik N Müller, Ralf Dechend, Florian Herse
RATIONALE: We hypothesized that cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. OBJECTIVE: Preeclamptic pregnancies feature hypertension, proteinuria, and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies...
June 24, 2016: Circulation Research
Dennis K Lee, Ori Nevo
Preeclampsia (PE) is a severe complication of pregnancy associated with maternal and fetal morbidity and mortality. The underlying pathophysiology involves maternal systemic vascular and endothelial dysfunction associated with circulating antiangiogenic factors, although the specific etiology of the disease remains elusive. Our aim was to investigate the maternal endothelium in PE by exploring the expression of genes involved with endothelial function in a novel platform of maternal primary endothelial cells...
June 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Yosuke Watanabe, Richard A Cohen, Reiko Matsui
Antioxidants are expected to improve cardiovascular disease (CVD) by eliminating oxidative stress, but clinical trials have not shown promising results in chronic CVD. Animal studies have revealed that reactive oxygen species (ROS) exacerbate acute CVDs in which high levels of ROS are observed. However, ROS are also necessary for angiogenesis after ischemia, because ROS not only damage cells but also stimulate the cell signaling required for angiogenesis. ROS affect signaling by protein modifications, especially of cysteine amino acid thiols...
May 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Chihiro Hirai, Motoi Sugimura, Shintaro Makino, Satoru Takeda
The production of soluble fms-like tyrosine kinase 1 (sFLT1) by exogenous chymotrypsin in trophoblast cells through protease-activated receptor (PAR) 2 was investigated to identify the role of a chymotrypsin-like serine protease in preeclampsia (PE) pathogenesis. We evaluated the expression of chymotrypsin, FLT1, and sFLT1 in monolayers of immortalized human trophoblast cells derived from placenta (TCL-1 cells). To investigate whether chymotrypsin enhances the production and release of sFLT1 through PAR-2, we examined changes in sFLT1 protein levels in conditioned medium by enzyme-linked immunosorbent assay and sFLT1 messenger RNA (mRNA) levels by real-time polymerase chain reaction in TCL-1 cells treated with exogenous chymotrypsin in the presence or absence of a PAR-2 antagonist or a chymotrypsin inhibitor (TPCK)...
May 2, 2016: Reproductive Sciences
Sajid Shahul, Diego Medvedofsky, Julia B Wenger, Junaid Nizamuddin, Samuel M Brown, Surichhya Bajracharya, Saira Salahuddin, Ravi Thadhani, Ariel Mueller, Avery Tung, Roberto M Lang, Zoltan Arany, Daniel Talmor, S Ananth Karumanchi, Sarosh Rana
Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng...
June 2016: Hypertension
Ana Jakovljevic, Mirjana Bogavac, Zagorka Lozanov-Crvenkovic, Mirjana Milosević-Tosic, Aleksandra Nikolic, Gorana Mitic
INTRODUCTION: Normal placental vascular development depends on multiple interaction of many regulatory molecules including pro and antiangiogenic proteins. It is considered that these vascular modulators might be one of the factors responsible for development hypertensive disorders in pregnancy. Objective was to evaluate and compare the early pregnancy (11.-14 week of gestation) serum level of angiogenic proteins sFlt1, VEGF i PIGF between different types of pregnancy related hypertensive disorders...
April 25, 2016: Journal of Maternal-fetal & Neonatal Medicine
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