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https://www.readbyqxmd.com/read/28335685/preterm-delivery-as-a-unique-pathophysiologic-state-characterized-by-maternal-soluble-fms-like-tyrosine-kinase-1-and-uterine-artery-resistance-during-pregnancy
#1
Jennifer K Straughen, Dawn P Misra, Laura Helmkamp, Vinod K Misra
BACKGROUND: Preterm delivery (PTD) may be characterized by altered interrelationships among angiogenic factors and measures of placental function. We analyzed the longitudinal relationship between maternal serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt1), an important antiangiogenic factor, and uterine artery resistance in pregnancies resulting in preterm and term deliveries. METHODS: Data were collected in a longitudinal cohort study involving 278 women monitored at 6 to 10, 10 to 14, 16 to 20, 22 to 26, and 32 to 36 weeks of gestation...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28325846/soluble-flt1-gene-therapy-alleviates-brain-arteriovenous-malformation-severity
#2
Wan Zhu, Fanxia Shen, Lei Mao, Lei Zhan, Shuai Kang, Zhengda Sun, Jeffrey Nelson, Rui Zhang, Dingquan Zou, Cameron M McDougall, Michael T Lawton, Thiennu H Vu, Zhijian Wu, Abraham Scaria, Peter Colosi, John Forsayeth, Hua Su
BACKGROUND AND PURPOSE: Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current therapies are associated with high morbidities. Excessive vascular endothelial growth factor has been implicated in bAVM pathophysiology. Because soluble FLT1 binds to vascular endothelial growth factor with high affinity, we tested intravenous delivery of an adeno-associated viral vector serotype-9 expressing soluble FLT1 (AAV9-sFLT1) to alleviate the bAVM phenotype...
March 21, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28299380/conditional-islet-hypovascularisation-does-not-preclude-beta-cell-expansion-during-pregnancy-in-mice
#3
Willem Staels, Yves Heremans, Gunter Leuckx, Naomi Van Gassen, Ciro Salinno, Sofie De Groef, Martine Cools, Eli Keshet, Yuval Dor, Harry Heimberg, Nico De Leu
AIMS/HYPOTHESIS: Endothelial-endocrine cell interactions and vascular endothelial growth factor (VEGF)-A signalling are deemed essential for maternal islet vascularisation, glucose control and beta cell expansion during mouse pregnancy. The aim of this study was to assess whether pregnancy-associated beta cell expansion was affected under conditions of islet hypovascularisation. METHODS: Soluble fms-like tyrosine kinase 1 (sFLT1), a VEGF-A decoy receptor, was conditionally overexpressed in maternal mouse beta cells from 1...
March 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/28262664/motor-neurons-control-blood-vessel-patterning-in-the-developing-spinal-cord
#4
Patricia Himmels, Isidora Paredes, Heike Adler, Andromachi Karakatsani, Robert Luck, Hugo H Marti, Olga Ermakova, Eugen Rempel, Esther T Stoeckli, Carmen Ruiz de Almodóvar
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF)...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28164532/clinical-assessment-of-soluble-fms-like-tyrosine-kinase-1-placental-growth-factor-ratio-for-the-diagnostic-and-the-prognosis-of-preeclampsia-in-the-second-trimester
#5
Dalenda Chelli, Asma Hamdi, Sarah Saoudi, Amel A Jenayah, Armand Zagre, Haithem Jguerim, Channoufi Bedis, Ezzeddine Sfar
BACKGROUND: Preeclampsia is one of the most common and serious complications of pregnancy. Various reports have demonstrated that disturbances in angiogenic and antiangiogenic factors are implicated in its pathogenesis and have possible relevance in its diagnosis and prognosis. METHODS: In this case-control study, we enrolled 73 patients with 34 preeclamptic cases diagnosed according to clinical criteria and dosing of proteinuria. The cases were matched to controls at the same age and parity...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28109704/nicotine-promotes-vascular-endothelial-growth-factor-secretion-by-human-trophoblast-cells-under-hypoxic-conditions-and-improves-the-proliferation-and-tube-formation-capacity-of-human-umbilical-endothelial-cells
#6
Hongbo Zhao, Lanxiang Wu, Yahui Wang, Jiayi Zhou, Ruixia Li, Jiabing Zhou, Zehua Wang, Congjian Xu
Pre-eclampsia, characterized as defective uteroplacental vascularization, remains the major cause of maternal and fetal mortality and morbidity. Previous epidemiological studies demonstrated that cigarette smoking reduced the risk of pre-eclampsia. However, the molecular mechanism remains elusive. In the present study, it is demonstrated that a low dose of nicotine decreased soluble vascular endothelial growth factor receptor 1 (sFlt1) secretion in human trophoblast cells under hypoxic conditions. Nicotine was then observed to promote vascular endothelial growth factor (VEGF) secretion by reducing sFlt1 secretion and increasing VEGF mRNA transcription...
January 17, 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28071661/neuronal-sflt1-and-vegfaa-determine-venous-sprouting-and-spinal-cord-vascularization
#7
Raphael Wild, Alina Klems, Masanari Takamiya, Yuya Hayashi, Uwe Strähle, Koji Ando, Naoki Mochizuki, Andreas van Impel, Stefan Schulte-Merker, Janna Krueger, Laetitia Preau, Ferdinand le Noble
Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28067578/relationship-between-hypoxia-and-downstream-pathogenic-pathways-in-preeclampsia
#8
Henri Augusto Korkes, Leandro De Oliveira, Nelson Sass, Saira Salahuddin, S Ananth Karumanchi, Augustine Rajakumar
Defects in angiogenesis and mitochondrial function in the placenta contribute to the pathogenesis of preeclampsia; however upstream regulators of these pathways are not known. It has been argued that placental hypoxia secondary to abnormal spiral artery remodeling may play a causal role in the angiogenic and mitochondrial abnormalities noted in preeclampsia. The aim of this study was to evaluate the relationship between hypoxia-inducible factor-1α (HIF-1α) ¸ a surrogate of hypoxia, and soluble fms-tyrosine kinase 1 (sFlt1), a circulating anti-angiogenic factor, and microRNA 210 (miR-210), a microRNA that regulates mitochondrial function, in human placentas from preeclamptic and non-hypertensive pregnancies...
January 9, 2017: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/28049536/usefulness-of-a-biomarker-to-identify-placental-dysfunction-in-the-context-of-malaria
#9
REVIEW
Alexandra Gueneuc, Philippe Deloron, Gwladys I Bertin
In most tropical areas, pregnant women are at increased risk of malaria, as a consequence of the massive sequestration of parasitized red blood cells in the placenta. The placenta plays a key role in embryonic and fetal development as well as in maternal-fetal exchanges, and pregnancy-associated malaria may alter selected placenta functions that lead to stillbirth and low birth weight. Although there are several tools (blood smear examination, RDT, PCR) to diagnose malaria infection during pregnancy, there is currently no test to assess placenta dysfunction in the framework of pregnancy-associated malaria...
January 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28039440/delivery-of-sfit-1-engineered-mscs-in-combination-with-a-continuous-low-dose-doxorubicin-treatment-prevents-growth-of-liver-cancer
#10
Jian Niu, Yue Wang, Ji Wang, Liu Bin, Xin Hu
One important process in liver cancer growth and progression is angiogenesis. Vascular endothelial growth factor (VEGF) has the significant role in liver cancer angiogenesis. sFlt1 (soluble Fms-like tyrosine kinase-1) is the promising inhibitor of VEGF and can be used as the new method of inhibiting angiogenesis. MSCs (Mesenchymal stem cells) can infiltrate into tumor tissue and function as the efficient transgene delivery mediator. Here, we engineered murine MSCs to express sFlt1 and examined the anti-tumor effect of MSC- sFlt1 in combination with continues low-dose doxorubicin treatment...
December 28, 2016: Aging
https://www.readbyqxmd.com/read/28029641/angiogenic-imbalance-and-residual-myocardial-injury-in-recovered-peripartum-cardiomyopathy-patients
#11
Sorel Goland, Jean Marc Weinstein, Adi Zalik, Rafael Kuperstein, Liaz Zilberman, Sara Shimoni, Michael Arad, Tuvia Ben Gal, Jacob George
BACKGROUND: Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM. METHODS AND RESULTS: Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61...
November 2016: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28000842/the-anti-angiogenic-role-of-soluble-form-vegf-receptor-in-malignant-gliomas
#12
Shingo Takano, Eiichi Ishikawa, Masahide Matsuda, Noriaki Sakamoto, Hiroyoshi Akutsu, Tetsuya Yamamoto, Akira Matsumura
Anti-angiogenic therapy represents a promising, new therapeutic modality for malignant gliomas. The present study was designed to define the malignant glioma cases most suitable for anti-angiogenic therapy and to demonstrate the efficacy of anti-angiogenic therapy using soluble-form Flt1 (sFlt1) gene delivery in mice. In human malignant glioma samples (39 glioblastomas, 21 anaplastic astrocytomas and 4 anaplastic oligoastrocytomas), protein expression of VEGF, and its specific natural inhibitor, sFlt1, as well as vessel architecture were assessed...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27939478/gelsolin-is-an-endogenous-inhibitor-of-syncytiotrophoblast-extracellular-vesicle-shedding-in-pregnancy
#13
Neil A Nadkarni, Augustine Rajakumar, Nikita Mokhashi, Suzanne D Burke, Sarosh Rana, Saira Salahuddin, Quynh Dang, Ravi Thadhani, Ramaswamy Krishnan, Thomas P Stossel, S Ananth Karumanchi
BACKGROUND: Preeclampsia, a pregnancy-specific inflammatory disorder, is characterized by high levels of anti-angiogenic protein, soluble fms-like tyrosine kinase 1 (sFlt1), in the maternal circulation. sFlt1 producing molecular machinery is present in syncytiotrophoblast extracellular vesicles that are released by the placenta into maternal plasma during normal pregnancy, a process greatly accelerated in preeclampsia. We hypothesized that syncytiotrophoblast extracellular vesicles exposes cytoplasmic actin to plasma resulting in depletion of plasma gelsolin (pGSN), an abundant plasma protein that scavenges circulating actin and other pro-inflammatory mediators...
October 2016: Pregnancy Hypertension
https://www.readbyqxmd.com/read/27939475/trophoblast-mitochondrial-function-is-impaired-in-preeclampsia-and-correlates-negatively-with-the-expression-of-soluble-fms-like-tyrosine-kinase-1
#14
Zsuzsanna K Zsengellér, Augustine Rajakumar, Jon T Hunter, Saira Salahuddin, Sarosh Rana, Isaac E Stillman, S Ananth Karumanchi
Preeclampsia is a common medical complication of pregnancy that is associated with significant morbidity and mortality to the mother and the baby. Extensive human epidemiological and experimental studies suggest that excess placental soluble fms-like tyrosine kinase 1, a potent anti-angiogenic factor leads to the maternal hypertension, proteinuria and other systemic complications of preeclampsia. To evaluate the mechanisms of the aberrant placental sFlt1 expression, we studied the role of mitochondrial dysfunction as one possible etiological factor...
October 2016: Pregnancy Hypertension
https://www.readbyqxmd.com/read/27927648/renin-angiotensin-system-transgenic-mouse-model-recapitulates-pathophysiology-similar-to-human-preeclampsia-with-renal-injury-that-may-be-mediated-through-vegf
#15
J Morgan Denney, Cynthia Bird, Annette Gendron-Fitzpatrick, Emmanuel Sampene, Ian M Bird, Dinesh M Shah
Using a transgenic cross, we evaluated features of preeclampsia, renal injury and the sFlt1/VEGF changes. Transgenic hAGT and hREN, or wild-type (WT) C57Bl/6 mice were cross-bred: female hAGT × male hREN for preeclampsia (PRE) model and female WT × male WT for pregnant controls (WTP). Samples were collected for plasma VEGF, sFlt1, and urine albumin. Blood pressures (BP) were monitored by telemetry. Vascular reactivity was investigated by wire myography. Kidneys and placenta were immunostained for sFlt1 and VEGF...
March 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27871476/steroid-sulfatase-is-increased-in-the-placentas-and-whole-blood-of-women-with-early-onset-preeclampsia
#16
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
https://www.readbyqxmd.com/read/27868196/differential-regulation-of-blood-flow-induced-neovascularization-and-mural-cell-recruitment-by-vascular-endothelial-growth-factor-and-angiopoietin-signalling
#17
Oliver A Stone, James G Carter, P Charles Lin, Ewa Paleolog, Maria J C Machado, David O Bates
KEY POINTS: Combining nitric oxide (NO)-mediated increased blood flow with angiopoietin-1-Tie2 receptor signalling induces arteriolargenesis - the formation of arterioles from capillaries - in a model of physiological angiogenesis. This NO-Tie-mediated arteriolargenesis requires endogenous vascular endothelial growth factor (VEGF) signalling. Inhibition of VEGF signalling increases pericyte coverage in microvessels. Together these findings indicate that generation of functional neovasculature requires close titration of NO-Tie2 signalling and localized VEGF induction, suggesting that the use of exogenous VEGF expression as a therapeutic for neovascularization may not be successful...
March 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27852438/radial-glia-regulate-vascular-patterning-around-the-developing-spinal-cord
#18
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
https://www.readbyqxmd.com/read/27791388/blood-laboratory-testing-for-early-prediction-of-preeclampsia-chasing-the-finish-line-or-at-the-starting-blocks
#19
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...
May 2017: Annals of Medicine
https://www.readbyqxmd.com/read/27737730/spatiotemporal-expression-profile-of-proteases-and-immunological-angiogenic-hormonal-and-apoptotic-mediators-in-rat-placenta-before-and-during-intrauterine-trophoblast-migration
#20
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
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