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Angiopoietins

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https://www.readbyqxmd.com/read/28545512/tie2-as-a-novel-key-factor-of-microangiopathy-in-systemic-sclerosis
#1
Falk Moritz, Janine Schniering, Jörg H W Distler, Renate E Gay, Steffen Gay, Oliver Distler, Britta Maurer
BACKGROUND: The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28542352/preconditioning-of-adipose-tissue-derived-mesenchymal-stem-cells-with-deferoxamine-increases-the-production-of-pro-angiogenic-neuroprotective-and-anti-inflammatory-factors-potential-application-in-the-treatment-of-diabetic-neuropathy
#2
Carolina Oses, Belén Olivares, Marcelo Ezquer, Cristian Acosta, Paul Bosch, Macarena Donoso, Patricio Léniz, Fernando Ezquer
Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors...
2017: PloS One
https://www.readbyqxmd.com/read/28539655/angiopoietin-1-enhances-neutrophil-chemotaxis-in-vitro-and-migration-in-vivo-through-interaction-with-cd18-and-release-of-ccl4
#3
Amanda Burnett, Ingrid Gomez, David Davila De Leon, Mark Ariaans, Pavlos Progias, Richard A Kammerer, Guillermo Velasco, Marie Marron, Paul Hellewell, Victoria Ridger
Angiopoietins are a family of growth factors that are ligands for the tyrosine kinase receptor, Tie2. Angiopoietin 1 (Ang-1) is agonistic for Tie2, plays a key role in blood vessel maturation and stability and has been shown to possess anti-inflammatory properties. However, Tie2 expression has been demonstrated on human neutrophils and the observation that neutrophils migrate in response to Ang-1 in vitro has confounded research into its exact role in inflammation as well as its potential use as a therapeutic agent...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28538136/genetic-and-pharmacologic-inactivation-of-angptl3-and-cardiovascular-disease
#4
Frederick E Dewey, Viktoria Gusarova, Richard L Dunbar, Colm O'Dushlaine, Claudia Schurmann, Omri Gottesman, Shane McCarthy, Cristopher V Van Hout, Shannon Bruse, Hayes M Dansky, Joseph B Leader, Michael F Murray, Marylyn D Ritchie, H Lester Kirchner, Lukas Habegger, Alex Lopez, John Penn, An Zhao, Weiping Shao, Neil Stahl, Andrew J Murphy, Sara Hamon, Aurelie Bouzelmat, Rick Zhang, Brad Shumel, Robert Pordy, Daniel Gipe, Gary A Herman, Wayne H H Sheu, I-Te Lee, Kae-Woei Liang, Xiuqing Guo, Jerome I Rotter, Yii-Der I Chen, William E Kraus, Svati H Shah, Scott Damrauer, Aeron Small, Daniel J Rader, Anders Berg Wulff, Børge G Nordestgaard, Anne Tybjærg-Hansen, Anita M van den Hoek, Hans M G Princen, David H Ledbetter, David J Carey, John D Overton, Jeffrey G Reid, William J Sasiela, Poulabi Banerjee, Alan R Shuldiner, Ingrid B Borecki, Tanya M Teslovich, George D Yancopoulos, Scott J Mellis, Jesper Gromada, Aris Baras
Background Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. Methods We sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies...
May 24, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28538111/cardiovascular-and-metabolic-effects-of-angptl3-antisense-oligonucleotides
#5
Mark J Graham, Richard G Lee, Teresa A Brandt, Li-Jung Tai, Wuxia Fu, Raechel Peralta, Rosie Yu, Eunju Hurh, Erika Paz, Bradley W McEvoy, Brenda F Baker, Nguyen C Pham, Andres Digenio, Steven G Hughes, Richard S Geary, Joseph L Witztum, Rosanne M Crooke, Sotirios Tsimikas
Background Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins. Methods We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1...
May 24, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28538018/low-serum-angiopoietin-1-high-serum-angiopoietin-2-and-high-ang-2-ang-1-protein-ratio-are-associated-with-early-onset-sepsis-in-surinamese-newborns
#6
Rens Zonneveld, Rianne Jongman, Amadu Juliana, Wilco Zijlmans, Frans Plötz, Grietje Molema, Matijs van Meurs
PURPOSE: Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and -2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. Levels of Ang-2 change in adults and children during sepsis, which is associated with severity of sepsis. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 hours after birth. METHODS: A prospective cohort study was performed amongst 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns...
May 22, 2017: Shock
https://www.readbyqxmd.com/read/28534941/two-natural-eudesmane-type-sesquiterpenes-from-laggera-alata-inhibit-angiogenesis-and-suppress-breast-cancer-cell-migration-through-vegf-and-angiopoietin-2-mediated-signaling-pathways
#7
Ning Liang, Yaolan Li, Hau Yin Chung
Eudesmane-type sesquiterpenes are natural sesquiterpenes with anti-inflammatory properties, but their anti-angiogenic activities are not known. The present study demonstrated that 5α-hydroxycostic acid and hydroxyisocostic acid, two eudesmane-type sesquiterpenes (ETSs), isolated from the herb Laggera alata, possessed anti-angiogenic effects. Under non-toxic dosage, ETSs suppressed VEGF‑induced proliferation in human umbilical vein endothelial cells (HUVECs) and vessel formation in zebrafish embryos. Moreover, ETSs inhibited VEGF-stimulated HUVEC migration, stress fibers and tube formation...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534127/genetics-of-triglycerides-and-the-risk-of-atherosclerosis
#8
REVIEW
Jacqueline S Dron, Robert A Hegele
PURPOSE OF REVIEW: Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality...
July 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28529319/therapeutic-targeting-of-the-angiopoietin-tie-pathway
#9
REVIEW
Pipsa Saharinen, Lauri Eklund, Kari Alitalo
The endothelial angiopoietin (ANG)-TIE growth factor receptor pathway regulates vascular permeability and pathological vascular remodelling during inflammation, tumour angiogenesis and metastasis. Drugs that target the ANG-TIE pathway are in clinical development for oncological and ophthalmological applications. The aim is to complement current vascular endothelial growth factor (VEGF)-based anti-angiogenic therapies in cancer, wet age-related macular degeneration and macular oedema. The unique function of the ANG-TIE pathway in vascular stabilization also renders this pathway an attractive target in sepsis, organ transplantation, atherosclerosis and vascular complications of diabetes...
May 19, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28528274/angiopoietin-like-8-angptl8-controls-adipocyte-lipolysis-and-phospholipid-composition
#10
Raghavendra Mysore, Gerhard Liebisch, You Zhou, Vesa M Olkkonen, P A Nidhina Haridas
Angiopoietin-like 8 (Angptl8) inhibits lipolysis in the circulation together with Angplt3 and controls post-prandial fat storage in white adipose tissue (WAT). It is strongly induced by insulin in vivo in WAT and in vitro in adipocytes. In this study we addressed the function of Angptl8 in adipocytes by its stable lentivirus-mediated knock-down in 3T3-L1 cells, followed by analyses of triglyceride (TG) storage, lipid droplet (LD) morphology, the cellular lipidome, lipolysis, and gene expression. Depletion of Angptl8 did not drastically affect the adipocytic differentiation of 3T3-L1 cells but resulted in a moderate (18-19%) reduction of stored TGs...
May 17, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28513569/intravenous-arginine-administration-promotes-proangiogenic-cells-mobilization-and-attenuates-lung-injury-in-mice-with-polymicrobial-sepsis
#11
Chiu-Li Yeh, Man-Hui Pai, Yao-Ming Shih, Juey-Ming Shih, Sung-Ling Yeh
This study investigated the influence of intravenous arginine (Arg) administration on alteration of circulating proangiogenic cells and remote lung injury in a model of polymicrobial sepsis. Mice were assigned to one normal control group (NC) and two sepsis groups that were induced by cecal ligation and puncture (CLP). One of the sepsis groups was injected with saline (SS), whereas the other (SA) was administered with a single bolus of 300 mg Arg/kg body weight via the tail vein 1 h after CLP. Septic mice were sacrificed at either 24 or 48 h after CLP, with their blood and lung tissues collected for analysis...
May 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28513544/morphogenetically-active-barrier-membrane-for-guided-bone-regeneration-based-on-amorphous-polyphosphate
#12
Xiaohong Wang, Maximilian Ackermann, Meik Neufurth, Shunfeng Wang, Heinz C Schröder, Werner E G Müller
We describe a novel regeneratively-active barrier membrane which consists of a durable electrospun poly(ε-caprolactone) (PCL) net covered with a morphogenetically-active biohybrid material composed of collagen and inorganic polyphosphate (polyP). The patch-like fibrous collagen structures are decorated with small amorphous polyP nanoparticles (50 nm) formed by precipitation of this energy-rich and enzyme-degradable (alkaline phosphatase) polymer in the presence of calcium ions. The fabricated PCL-polyP/collagen hybrid mats are characterized by advantageous biomechanical properties, such as enhanced flexibility and stretchability with almost unaltered tensile strength of the PCL net...
May 17, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28508859/plastic-roles-of-pericytes-in-the-blood-retinal-barrier
#13
Do Young Park, Junyeop Lee, Jaeryung Kim, Kangsan Kim, Seonpyo Hong, Sangyeul Han, Yoshiaki Kubota, Hellmut G Augustin, Lei Ding, Jin Woo Kim, Hail Kim, Yulong He, Ralf H Adams, Gou Young Koh
The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507810/tie-2-expressing-monocytes-in-human-cancers
#14
Riccardo Turrini, Angélique Pabois, Ioannis Xenarios, George Coukos, Jean-François Delaloye, Marie-Agnès Doucey
Tumor-associated macrophages (TAM) are well known as a key player in the tumor microenvironment, which support cancer progression. More recently, a lineage of monocytes characterized by the expression of the TIE-2/Tek angiopoietin receptor identified a subset of circulating and tumor-associated monocytes endowed with proangiogenic activity. TIE-2 expressing monocytes (TEM) were found both in humans and mice. Here, we review the phenotypes and functions of TEM reported so far in human cancer and their potential use as markers of cancer progression and metastasis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28502557/antecedents-and-early-correlates-of-high-and-low-concentrations-of-angiogenic-proteins-in-extremely-preterm-newborns
#15
Alan Leviton, Stanthia Ryan, Elizabeth N Allred, Raina N Fichorova, T Michael O'Shea, Karl Kuban, Olaf Dammann
BACKGROUND: To identify the antecedents and very early correlates of low concentrations of angiogenic proteins in the blood of extremely preterm newborns during the first postnatal month. METHODS: Using multiplex immunoassays we measured the concentrations of vascular endothelial growth factor A (VEGF), VEGF receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), placenta growth factor (PIGF), and angiopoietins 1 and 2 (Ang-1, Ang-2), as well as 21 other proteins in blood spots collected on postnatal days 1 (N=1062), 7 (N=1087), 14 (N=989), 21 (N=940) and 28 (N=880) from infants born before the 28th week of gestation...
May 11, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28502512/metreleptin-therapy-lowers-plasma-angiopoietin-like-protein-3-in-patients-with-generalized-lipodystrophy
#16
Ranganath Muniyappa, Brent S Abel, Asha Asthana, Mary F Walter, Elaine K Cochran, Alan T Remaley, Monica C Skarulis, Phillip Gorden, Rebecca J Brown
BACKGROUND: Reduced triglyceride clearance due to impaired lipoprotein lipase-mediated lipolysis contributes to severe hypertriglyceridemia in lipodystrophy. Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) impair clearance of triglycerides by inhibiting lipoprotein lipase. Whether circulating ANGPTL3/4 levels are altered in lipodystrophy and the effects of leptin replacement on these ANGPTLs are unknown. OBJECTIVE: To examine if ANGPTL3/4 levels are elevated in patients with generalized lipodystrophy and assess the effects of leptin replacement on these ANGPTLs...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28502137/angiopoietin-2-as-a-biomarker-for-echocardiographic-abnormalities-and-carotid-atherosclerosis-in-rheumatoid-arthritis-patients
#17
Hanan Omar, Ahmed Tageldien Abdellah, Housseini Abdalla, Samah Ismail Nasef, Hamdy Omar
Atherosclerosis and cardiovascular diseases (CVD) are increasingly recognised complications of rheumatoid arthritis (RA). Angiopoietin 2 (Ang-2) levels have been associated with clinically overt CVD in general population; we assessed serum Ang-2 levels and its correlation with Echocardiographic abnormalities and carotid intima-media thickness in RA patients. 44 RA patients without clinically overt CVD and 44 healthy controls were assessed by questionnaire and clinical examination. Disease activity score (DAS-28) was calculated...
June 2016: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/28498260/combined-gene-therapy-using-adsvegfr2-and-adstie2-with-chemotherapy-reduces-the-growth-of-human-ovarian-cancer-and-formation-of-ascites-in-mice
#18
Laura Tuppurainen, Hanna Sallinen, Anni Karvonen, Elina Valkonen, Hanne Laakso, Timo Liimatainen, Elisa Hytönen, Kirsi Hämäläinen, Veli-Matti Kosma, Maarit Anttila, Seppo Ylä-Herttuala
OBJECTIVES: Ovarian cancer is highly dependent on tumor microvessels and angiogenesis regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) and angiopoietins (Ang) and their Tie receptors. We studied the efficacy of adenoviral (Ad) gene therapy with soluble VEGFR2 and Tie2 combined with paclitaxel and carboplatin for the treatment of ovarian cancer. METHODS: An intraperitoneal human ovarian cancer xenograft model in nude mice (n = 44) was used in this study...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28497874/serum-angiopoietin-2-level-as-a-potential-biomarker-in-psoriasis-vulgaris
#19
Takehiro Takahashi, Yoshihide Asano, Sayaka Shibata, Yayoi Tada, Shinichi Sato
No abstract text is available yet for this article.
February 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28494191/biomarker-for-early-renal-microvascular-and-diabetic-kidney-diseases
#20
Narisa Futrakul, Prasit Futrakul
Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m(2), is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II)...
November 2017: Renal Failure
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