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soluble tyrosine kinase 1

Mark W Cunningham, Javier Castillo, Tarek Ibrahim, Denise C Cornelius, Nathan Campbell, Lorena Amaral, Venkata Ramana Vaka, Nathan Usry, Jan M Williams, Babbette LaMarca
Women with preeclampsia produce AT1-AA (agonistic autoantibodies to the angiotensin II type 1 receptor), which stimulate reactive oxygen species, inflammatory factors, and hypertensive mechanisms (ET [endothelin] and sFlt-1 [soluble fms-like tyrosine kinase-1]) in rodent models of preeclampsia. The placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits many of these features. In this study, we examined the maternal outcomes of AT1-AA inhibition ('n7AAc') in RUPP rats...
March 19, 2018: Hypertension
Hiroko Tanaka, Keiichi Kumasawa, Aiko Kakigano, Kazuya Mimura, Masayuki Endo, Takuji Tomimatsu, Tadashi Kimura
Excessive soluble fms-like tyrosine kinase-1 (sFlt-1) has been strongly implicated in preeclampsia. An increase in the serum sFlt-1 level occurs before the onset of preeclampsia, and the sFlt-1 level is already higher in women who are predisposed to preeclampsia than in normotensive pregnant women. This study aimed to investigate the relation between arginase and sFlt-1 in the plasma of preeclamptic women and normotensive pregnant women. We suggested that a regulatory mechanism exists that suppresses the level of sFlt-1...
March 13, 2018: Biochemical and Biophysical Research Communications
Clara Barneo-Caragol, Eduardo Martínez-Morillo, Susana Rodríguez-González, Paloma Lequerica-Fernández, Ignacio Vega-Naredo, Francisco V Álvarez Menéndez
BACKGROUND: Preeclampsia (PE) is considered a specific vascular disease in which endothelial dysfunction may be the crucial factor of its pathogenesis. It has been suggested that strontium (Sr) may play a role in the pathophysiology of PE. Our group established in a previous study the serum levels of Sr in healthy pregnancies, and the main aim of the present study was to evaluate Sr concentrations and oxidative status in preeclamptic women. METHODS: The study population included women with early-onset PE (E-PE, n = 39), late-onset PE (L-PE, n = 67) and serial samples from a subset of preeclamptic women (PE-ss, n = 20)...
May 2018: Journal of Trace Elements in Medicine and Biology
Charikleia Kelaidi, Antonis Kattamis, Filia Apostolakou, Christos Poziopoulos, Christina Lazaropoulou, Polyxeni Delaporta, Ino Kanavaki, Ioannis Papassotiriou
BACKGROUND: Levels of the angiogenic cytokines Placental Growth Factor (PlGF) and soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in Sickle Cell Disease and iron overload, but they have not been evaluated in Non-Transfusion-Dependent Thalassemia (NTDT). PATIENTS AND METHODS: We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation and tissue hypoxia...
March 15, 2018: European Journal of Haematology
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
Yvonne Kwun Yue Cheng, Lai Wa Law, Tak Yeung Leung, Oi Ka Chan, Daljit Singh Sahota
OBJECTIVE: To assess the clinical utility of the sFlt-1:PlGF ratio rule-in/rule-out pre-eclampsia either directly or after correcting each marker for gestation and maternal weight. METHODS: This was a prospective cohort study. sFlt-1, PlGF were measured in 965 women randomized to undergo a single blood withdraw between 20 and 39 weeks of gestation. sFlt-1, PlGF and the sFlt-1:PlGF ratio temporal relationship was determined. sFlt-1 and PlGF were converted to multiples of the expected gestational median (MoM) and adjusted for maternal weight...
January 2018: Pregnancy Hypertension
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
Dorien Reijnders, Chin-Chi Liu, Xinjing Xu, Anna Zhao, Kelsey Olson, Scott D Butler, Nataki C Douglas, Jenny L Sones
Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface...
March 9, 2018: Physiological Genomics
Rungnapa Ruchob, Julienne N Rutherford, Aleeca F Bell
BACKGROUND: Neonates born small for gestational age (SGA) face increased risk of neonatal mortality, childhood developmental problems, and adult disease. The placenta is a key factor in SGA development because of its multiple biological processes that underlie fetal growth. However, valid and reliable placental biomarkers of SGA have not been determined. OBJECTIVES: The objective of this article was to systematically identify and review studies examining associations between placental biomarkers and SGA and assess those biomarkers' predictive value...
January 1, 2018: Biological Research for Nursing
Janina Müller-Deile, Patricia Schröder, Lynne Beverly-Staggs, Rebecca Hiss, Jan Fiedler, Jenny Nyström, Thomas Thum, Hermann Haller, Mario Schiffer
So far the pathomechanism of preeclampsia in pregnancy is focussed on increased circulating levels of soluble fms-like tyrosin kinase-1 (sFLT-1) that neutralizes glomerular VEGF-A expression and prevents its signaling at the glomerular endothelium. As a result of changed glomerular VEGF-A levels endotheliosis and podocyte foot process effacement are typical morphological features of preeclampsia. Recently, microRNA-26a-5p (miR-26a-5p) was described to be also upregulated in the preeclamptic placenta. We found that miR-26a-5p targets VEGF-A expression by means of PIK3C2α in cultured human podocytes and that miR-26a-5p overexpression in zebrafish causes proteinuria, edema, glomerular endotheliosis and podocyte foot process effacement...
February 26, 2018: Scientific Reports
S Ananth Karumanchi
More than a decade ago, circulating anti-angiogenic factors of placental origin were implicated in the pathogenesis of preeclampsia (Karumanchi SA. Hypertension. 2016 Jun;67(6):1072-9). In particular, circulating soluble fms-like tyrosine kinase 1 (sFlt-1), an anti-angiogenic factor that inhibits vascular endothelial growth factor (VEGF) signaling has been extensively studied in humans and in animal models of preeclampsia. Epidemiological, experimental and genetic studies point to a causal role for sFlt1 in the etiology of the disease...
February 23, 2018: BJOG: An International Journal of Obstetrics and Gynaecology
Michael C Honigberg, Ellen W Seely, Ann M Thomas, Kee-Hak Lim, Samuel Parry, Thomas F McElrath
OBJECTIVE: To assess the effect of infant size as a marker of placental function on the association between preeclampsia and the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF). STUDY DESIGN: The angiogenic factors sFlt-1 and PlGF were measured prospectively at 26 weeks gestation in 2322 women. Pregnancies were stratified by whether or not they were complicated by preeclampsia, the timing of delivery, and birthweight Z-score...
February 21, 2018: Journal of Perinatology: Official Journal of the California Perinatal Association
Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Sally Beard, Ping Cannon, Roxanne Hastie, Tuong V Nguyen, Natalie K Binder, Stephen Tong, Natalie J Hannan
INTRODUCTION: The discovery of new treatments that prevent or treat preeclampsia would be a major advance. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG) are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. We recently identified metformin and esomeprazole as potential treatments for preeclampsia. Both reduce placental and endothelial secretion of sFlt-1 and soluble endoglin, and reduce endothelial dysfunction...
2018: PloS One
Tuangsit Wataganara, Jarunee Leetheeragul, Suchittra Pongprasobchai, Anuwat Sutantawibul, Chayawat Phatihattakorn, Surasak Angsuwathana
The benefit of the early administration of aspirin to reduce preterm pre-eclampsia among screened positive European women from multivariate algorithmic approach (ASPRE trial) has opened an intense debate on the feasibility of universal screening. This review aims to assess the new perspectives in the combined screening of pre-eclampsia in the first trimester of pregnancy and the chances for prevention using low-dose aspirin with special emphasis on the particularities of the Asian population. PubMed, CENTRAL and Embase databases were searched from inception until 15 November 2017 using combinations of the search terms: preeclampsia, Asian, prenatal screening, early prediction, ultrasonography, pregnancy, biomarker, mean arterial pressure, soluble fms-like tyrosine kinase-1, placental growth factor, pregnancy-associated plasma protein-A and pulsatility index...
February 14, 2018: Journal of Obstetrics and Gynaecology Research
Chunhua Zhang, Yong Zhu, Yan Shen, Changting Zuo
Reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) in the placenta was found in women with severe preeclampsia. Aspirin is currently used as the only recommended intervention in pregnancies for prevention of preeclampsia. In this study, we aimed to investigate whether aspirin could attenuate PPARγ inhibitor (T0070907)-induced preeclampsia and its impact on expression of PPARγ. Sixty Sprague-Dawley rats were used and treated with different doses of aspirin (0, 1, and 1.5 mg/kg) in presence or absence of PPARγ antagonist, T0070907...
January 1, 2018: Reproductive Sciences
Irene Scharf, Lisa Bierbaumer, Heidemarie Huber, Philipp Wittmann, Christine Haider, Christine Pirker, Walter Berger, Wolfgang Mikulits
Genomic editing using the CRISPR/Cas9 technology allows selective interference with gene expression. With this method, a multitude of haploid and diploid cells from different organisms have been employed to successfully generate knockouts of genes coding for proteins or small RNAs. Yet, cancer cells exhibiting an aberrant ploidy are considered to be less accessible to CRISPR/Cas9-mediated genomic editing, as amplifications of the targeted gene locus could hamper its effectiveness. Here we examined the suitability of CRISPR/Cas9 to knockout the receptor tyrosine kinase Axl in the human hepatoma cell lines HLF and SNU449...
February 2018: Oncology Letters
Elisabeth A Schuldt, Wolfgang Lieb, Marcus Dörr, Markus M Lerch, Henry Völzke, Matthias Nauck, Nele Friedrich
BACKGROUND: The Angiopoietin/Tie (Tyrosine kinase with Ig and EGF homology domains) signaling axis has crucial influences on angiogenesis and the vasculature's reorganization. Moreover, angiopoietin-2 (Ang2) is discussed as a biomarker for diseases' severity and development. Previous studies reported increased Ang2 levels in patients with inflammatory diseases and associations of Ang2 with inflammation markers in relatively small samples. We aimed to assess the relation of Ang2 and Tie2 with inflammation markers in the general population...
February 7, 2018: Cytokine
Michiko Yamashita, Keiichi Kumasawa, Hitomi Nakamura, Tadashi Kimura
INTRODUCTION: Placenta previa is an abnormality in which the placenta covers the internal uterine os, and it can cause serious morbidity and mortality in both mother and fetus due to catastrophic hemorrhage. Some pregnant women recover from placenta previa due to a phenomenon called "migration." However, the mechanism of "migration" of the placenta has not been elucidated. METHODS: Human placentas were collected from patients with placenta previa and those with no abnormal placentation (control)...
January 30, 2018: Biochemical and Biophysical Research Communications
Jun Liu, Bing Liu, Sufen Chen, Ben-Qiang Gong, Lijuan Chen, Qi Zhou, Feng Xiong, Menglong Wang, Dongru Feng, Jian-Feng Li, Hong-Bin Wang, Jinfa Wang
Plants initiate immunity by cell-surface pattern-recognition receptors (PRRs), which perceive non-self molecules. PRRs are predominantly receptor serine/threonine (Ser/Thr) kinases that are evolutionarily related to animal interleukin-1 receptor-associated kinase (IRAK)/Pelle-soluble kinases. However, how the activity of these receptor kinases is modulated remains poorly understood. We report that the Arabidopsis PRR chitin elicitor receptor kinase 1 (CERK1) is autophosphorylated in unstimulated cells at tyrosine 428 (Tyr 428 ), a modification that is required for CERK1 activation upon binding to the fungal cell wall component chitin...
February 14, 2018: Cell Host & Microbe
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