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https://www.readbyqxmd.com/read/29346025/linkage-of-metabolic-defects-to-activated-pik3ca-alleles-in-endothelial-cells-derived-from-lymphatic-malformation
#1
Kathryn Glaser, Peter Dickie, Derek Neilson, Alexander Osborn, Belinda Hsi Dickie
BACKGROUND: Lymphatic endothelial cells (LECs) derived from lymphatic malformations (LMs) bear activated PIK3CA alleles yet display an inflammatory gene expression profile. A basis for the inflammatory phenotype was sought by screening for coexisting somatic mutations. METHODS AND RESULTS: Fourteen independent LEC populations bearing activated PIK3CA alleles were isolated from LM. These were characterized by the expression of growth and inflammatory genes (VEGFC, IL-6, COX-2, IL-8, HO-1, E-SEL) by qRT-PCR...
January 18, 2018: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/29339422/the-role-of-angiopoietin-like-protein-4-in-phenylephrine-induced-cardiomyocyte-hypertrophy
#2
Yu Sun, Yi Li, Chen Liu, Ruicong Xue, Bin Dong, Huiling Huang, Longyun Peng, Jun Liu, Yugang Dong
Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional secreted protein that can be induced by fasting, hypoxia and glucocorticoids. ANGPTL4 has been associated with a variety of diseases, however, the role of ANGPTL4 in cardiac hypertrophy remains poorly understood. In our study, we aimed to explore the effect of ANGPTL4 on phenylephrine (PE)-induced cardiomyocyte hypertrophy. Our results showed that knockdown of ANGPTL4 expression significantly exacerbated cardiomyocyte hypertrophy, as demonstrated by increased hypertrophic marker expression, including ANP and cell surface area...
January 16, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29304116/the-sorafenib-anti-relapse-effect-after-allohsct-is-associated-with-heightened-alloreactivity-and-accumulation-of-cd8-pd-1-cd279-lymphocytes-in-marrow
#3
Andrzej Lange, Emilia Jaskula, Janusz Lange, Grzegorz Dworacki, Dorota Nowak, Aleksandra Simiczyjew, Monika Mordak-Domagala, Mariola Sedzimirska
We studied three FLT3 ITD acute myeloid leukemia (AML) patients who relapsed after allogeneic haematopoietic stem cell transplantation (alloHSCT) and received multikinase inhibitor (MKI) sorafenib as part of salvage therapy. MKI was given to block the effect of FLT3 ITD mutation which powers proliferation of blast cells. However, the known facts that sorafenib is more effective in patents post alloHSCT suggested that this MKI can augment the immune system surveillance on leukaemia. In the present study, we investigated in depth the effect of sorafenib on the alloreactivity seen post-transplant including that on leukaemia...
2018: PloS One
https://www.readbyqxmd.com/read/29221972/angiopoietin-like-proteins-4-angptl4-gene-polymorphisms-and-risk-of-brain-arteriovenous-malformation
#4
Sarafroz A Erkinova, Ekaterina A Sokolova, Kirill Y Orlov, Vitaly S Kiselev, Nikolay V Strelnikov, Andrey V Dubovoy, Elena N Voronina, Maxim L Filipenko
BACKGROUND: Brain arteriovenous malformations (BAVMs) are formed by hypertrophied arterial vessels (afferents, feeders), a large number of arteriovenous shunts which become tangled to form a body (nidus) of malformation, which then expands draining proximal veins. The aim of this study was a replication of single nucleotide polymorphism (SNP) rs11672433 association with BAVM development with the subsequent meta-analysis of published data. METHODS: A total of 252 Russian patients with brain BAVMs and 480 control subjects were included in the present study...
December 5, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29193797/the-long-non-coding-rna-pvt1-represses-angptl4-transcription-through-binding-with-ezh2-in-trophoblast-cell
#5
Yetao Xu, Yifan Lian, Yuanyuan Zhang, Shiyun Huang, Qing Zuo, Nana Yang, Yanzi Chen, Dan Wu, Lizhou Sun
Despite progress in diagnostics and treatment for preeclampsia, it remains the foremost cause of maternal and foetal perinatal morbidity and mortality worldwide. Over recent years, various lines of evidence have emphasized long non-coding RNAs (lncRNAs) which function as an innovative regulator of biological behaviour, as exemplified by proliferation, apoptosis and metastasis. However, the role of lncRNAs has not been well described in preeclampsia. Here, we identified a lncRNA, PVT1, whose expression was down-regulated in qRT-PCR analyses in severe preeclampsia...
November 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29191809/molecular-fingerprint-for-terminal-abdominal-aortic-aneurysm-disease
#6
Gabor Gäbel, Bernd H Northoff, Irina Weinzierl, Stefan Ludwig, Irene Hinterseher, Wolfgang Wilfert, Daniel Teupser, Stefan A Doderer, Hendrik Bergert, Frank Schönleben, Jan H N Lindeman, Lesca M Holdt
BACKGROUND: Clinical decision making in abdominal aortic aneurysms (AAA) relies completely on diameter. At this point, improved decision tools remain an unmet medical need. Our goal was to identify changes at the molecular level specifically leading up to AAA rupture. METHODS AND RESULTS: Aortic wall tissue specimens were collected during open elective (eAAA; n=31) or emergency repair of ruptured AAA (rAAA; n=17), and gene expression was investigated using microarrays...
November 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29191670/short-term-cooling-increases-serum-angiopoietin-like-4-levels-in-healthy-lean-men
#7
Kimberly J Nahon, Geerte Hoeke, Leontine E H Bakker, Ingrid M Jazet, Jimmy F P Berbée, Sander Kersten, Patrick C N Rensen, Mariëtte R Boon
BACKGROUND: Cold exposure enhances sympathetic outflow to peripheral tissues, thereby stimulating intracellular lipolysis in white adipose tissue and increasing the lipoprotein lipase-dependent uptake and combustion of triglyceride-derived fatty acids (FAs) by brown adipose tissue. Angiopoietin-like 4 (ANGPTL4) inhibits lipoprotein lipase and can be regulated by cold exposure, at least in mice. OBJECTIVE: In the present study, we examined the effect of short-term mild cooling on serum ANGPTL4 levels in healthy lean men of White Caucasian and South Asian descent...
November 1, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29177891/plasma-levels-of-hypoxia-regulated-factors-in-patients-with-age-related-macular-degeneration
#8
Zygoula Ioanna, Schori Christian, Grimm Christian, Barthelmes Daniel
PURPOSE: Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. METHODS: Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11)...
November 25, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/29133941/bladder-cancer-context-is-key-dual-roles-of-angptl4
#9
Louise Stone
No abstract text is available yet for this article.
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29123172/transcriptomic-and-epigenetic-responses-to-short-term-nutrient-exercise-stress-in-humans
#10
R C Laker, C Garde, D M Camera, W J Smiles, J R Zierath, J A Hawley, R Barrès
High fat feeding impairs skeletal muscle metabolic flexibility and induces insulin resistance, whereas exercise training exerts positive effects on substrate handling and improves insulin sensitivity. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100268/angptl4-promotes-the-progression-of-cutaneous-melanoma-to-brain-metastasis
#11
Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz
In an ongoing effort to identify molecular determinants regulating melanoma brain metastasis, we previously identified Angiopoietin-like 4 (ANGPTL4) as a component of the molecular signature of such metastases. The aim of this study was to determine the functional significance of ANGPTL4 in the shaping of melanoma malignancy phenotype, especially in the establishment of brain metastasis. We confirmed that ANGPTL4 expression is significantly higher in cells metastasizing to the brain than in cells from the cutaneous (local) tumor from the same melanoma in a nude mouse xenograft model, and also in paired clinical specimens of melanoma metastases than in primary melanomas from the same patients...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100106/l-mimosine-and-hypoxia-enhance-angiopoietin-like-4-production-involving-hypoxia-inducible-factor-1alpha-insights-from-monolayer-and-spheroid-cultures-of-dental-pulp-derived-cells-and-tooth-slice-cultures
#12
Klara Janjić, Umar Alhujazy, Andreas Moritz, Hermann Agis
OBJECTIVE: Angiopoietin-like 4 (Angptl4) is an angiogenesis modulating signaling factor and as such involved in blood vessel formation but also in hard tissue resorption. Here we hypothesized that the hypoxia mimetic agent L-mimosine (L-MIM) and hypoxia stimulate the production of Angptl4 in the dental pulp. MATERIAL AND METHODS: Monolayer and spheroid cultures of primary human dental pulp-derived cells (DPC) were treated with L-MIM or hypoxia. Furthermore, tooth slice cultures were performed...
October 16, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29083408/exome-wide-association-study-of-plasma-lipids-in-300-000-individuals
#13
Dajiang J Liu, Gina M Peloso, Haojie Yu, Adam S Butterworth, Xiao Wang, Anubha Mahajan, Danish Saleheen, Connor Emdin, Dewan Alam, Alexessander Couto Alves, Philippe Amouyel, Emanuele Di Angelantonio, Dominique Arveiler, Themistocles L Assimes, Paul L Auer, Usman Baber, Christie M Ballantyne, Lia E Bang, Marianne Benn, Joshua C Bis, Michael Boehnke, Eric Boerwinkle, Jette Bork-Jensen, Erwin P Bottinger, Ivan Brandslund, Morris Brown, Fabio Busonero, Mark J Caulfield, John C Chambers, Daniel I Chasman, Y Eugene Chen, Yii-Der Ida Chen, Rajiv Chowdhury, Cramer Christensen, Audrey Y Chu, John M Connell, Francesco Cucca, L Adrienne Cupples, Scott M Damrauer, Gail Davies, Ian J Deary, George Dedoussis, Joshua C Denny, Anna Dominiczak, Marie-Pierre Dubé, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Aliki-Eleni Farmaki, Mary F Feitosa, Marco Ferrario, Jean Ferrieres, Ian Ford, Myriam Fornage, Paul W Franks, Timothy M Frayling, Ruth Frikke-Schmidt, Lars G Fritsche, Philippe Frossard, Valentin Fuster, Santhi K Ganesh, Wei Gao, Melissa E Garcia, Christian Gieger, Franco Giulianini, Mark O Goodarzi, Harald Grallert, Niels Grarup, Leif Groop, Megan L Grove, Vilmundur Gudnason, Torben Hansen, Tamara B Harris, Caroline Hayward, Joel N Hirschhorn, Oddgeir L Holmen, Jennifer Huffman, Yong Huo, Kristian Hveem, Sehrish Jabeen, Anne U Jackson, Johanna Jakobsdottir, Marjo-Riitta Jarvelin, Gorm B Jensen, Marit E Jørgensen, J Wouter Jukema, Johanne M Justesen, Pia R Kamstrup, Stavroula Kanoni, Fredrik Karpe, Frank Kee, Amit V Khera, Derek Klarin, Heikki A Koistinen, Jaspal S Kooner, Charles Kooperberg, Kari Kuulasmaa, Johanna Kuusisto, Markku Laakso, Timo Lakka, Claudia Langenberg, Anne Langsted, Lenore J Launer, Torsten Lauritzen, David C M Liewald, Li An Lin, Allan Linneberg, Ruth J F Loos, Yingchang Lu, Xiangfeng Lu, Reedik Mägi, Anders Malarstig, Ani Manichaikul, Alisa K Manning, Pekka Mäntyselkä, Eirini Marouli, Nicholas G D Masca, Andrea Maschio, James B Meigs, Olle Melander, Andres Metspalu, Andrew P Morris, Alanna C Morrison, Antonella Mulas, Martina Müller-Nurasyid, Patricia B Munroe, Matt J Neville, Jonas B Nielsen, Sune F Nielsen, Børge G Nordestgaard, Jose M Ordovas, Roxana Mehran, Christoper J O'Donnell, Marju Orho-Melander, Cliona M Molony, Pieter Muntendam, Sandosh Padmanabhan, Colin N A Palmer, Dorota Pasko, Aniruddh P Patel, Oluf Pedersen, Markus Perola, Annette Peters, Charlotta Pisinger, Giorgio Pistis, Ozren Polasek, Neil Poulter, Bruce M Psaty, Daniel J Rader, Asif Rasheed, Rainer Rauramaa, Dermot F Reilly, Alex P Reiner, Frida Renström, Stephen S Rich, Paul M Ridker, John D Rioux, Neil R Robertson, Dan M Roden, Jerome I Rotter, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Serena Sanna, Naveed Sattar, Ellen M Schmidt, Robert A Scott, Peter Sever, Raquel S Sevilla, Christian M Shaffer, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S Small, Albert V Smith, Blair H Smith, Sangeetha Somayajula, Lorraine Southam, Timothy D Spector, Elizabeth K Speliotes, John M Starr, Kathleen E Stirrups, Nathan Stitziel, Konstantin Strauch, Heather M Stringham, Praveen Surendran, Hayato Tada, Alan R Tall, Hua Tang, Jean-Claude Tardif, Kent D Taylor, Stella Trompet, Philip S Tsao, Jaakko Tuomilehto, Anne Tybjaerg-Hansen, Natalie R van Zuydam, Anette Varbo, Tibor V Varga, Jarmo Virtamo, Melanie Waldenberger, Nan Wang, Nick J Wareham, Helen R Warren, Peter E Weeke, Joshua Weinstock, Jennifer Wessel, James G Wilson, Peter W F Wilson, Ming Xu, Hanieh Yaghootkar, Robin Young, Eleftheria Zeggini, He Zhang, Neil S Zheng, Weihua Zhang, Yan Zhang, Wei Zhou, Yanhua Zhou, Magdalena Zoledziewska, Joanna M M Howson, John Danesh, Mark I McCarthy, Chad A Cowan, Goncalo Abecasis, Panos Deloukas, Kiran Musunuru, Cristen J Willer, Sekar Kathiresan
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD...
October 30, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29056962/chiglitazar-preferentially-regulates-gene-expression-via-configuration-restricted-binding-and-phosphorylation-inhibition-of-ppar%C3%AE
#14
De-Si Pan, Wei Wang, Nan-Song Liu, Qian-Jiao Yang, Kun Zhang, Jing-Zhong Zhu, Song Shan, Zhi-Bin Li, Zhi-Qiang Ning, Laiqiang Huang, Xian-Ping Lu
Type 2 diabetes mellitus is often treated with insulin-sensitizing drugs called thiazolidinediones (TZD), which improve insulin resistance and glycemic control. Despite their effectiveness in treating diabetes, these drugs provide little protection from eminent cardiovascular disease associated with diabetes. Here we demonstrate how chiglitazar, a configuration-restricted non-TZD peroxisome proliferator-activated receptor (PPAR) pan agonist with moderate transcription activity, preferentially regulates ANGPTL4 and PDK4, which are involved in glucose and lipid metabolism...
2017: PPAR Research
https://www.readbyqxmd.com/read/29035390/epigenetic-silencing-of-the-dual-role-signal-mediator-angptl4-in-tumor-tissues-and-its-overexpression-in-the-urothelial-carcinoma-microenvironment
#15
H-Y Hsieh, Y-C Jou, C-L Tung, Y-S Tsai, Y-H Wang, C-L Chi, R-I Lin, S-K Hung, Y-M Chuang, S-F Wu, C Li, C-H Shen, M W Y Chan, C-D Hsu
Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell lines we examined. Previous studies had demonstrated that ANGPTL4 is highly expressed in some cancers, but downregulated, by DNA methylation, in others. Consequently, owing to these seemingly conflicting functions in distinct cancers, the precise role of ANGPTL4 in the etiology of UC remains unclear...
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29033534/multicellular-tumor-spheroids-of-human-uveal-melanoma-induce-genes-associated-with-anoikis-resistance-lipogenesis-and-ssxs
#16
Charlotte Ness, Øystein Garred, Nils A Eide, Theresa Kumar, Ole K Olstad, Thomas P Bærland, Goran Petrovski, Morten C Moe, Agate Noer
PURPOSE: Uveal melanoma (UM) has a high propensity for metastatic spread, and approximately 40-50% of patients die of metastatic disease. Metastases can be found at the time of diagnosis but also several years after the tumor has been removed. The survival of disseminated cancer cells is known to be linked to anchorage independence, anoikis resistance, and an adaptive cellular metabolism. The cultivation of cancer cells as multicellular tumor spheroids (MCTS) by anchorage-independent growth enriches for a more aggressive phenotype...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29031727/angiopoietin-like-protein-4-is-an-exercise-induced-hepatokine-in-humans-regulated-by-glucagon-and-camp
#17
Bodil Ingerslev, Jakob S Hansen, Christoph Hoffmann, Jens O Clemmesen, Niels H Secher, Mika Scheler, Martin Hrabĕ de Angelis, Hans U Häring, Bente K Pedersen, Cora Weigert, Peter Plomgaard
OBJECTIVE: Angiopoietin-like protein-4 (ANGPTL4) is a circulating protein that is highly expressed in liver and implicated in regulation of plasma triglyceride levels. Systemic ANGPTL4 increases during prolonged fasting and is suggested to be secreted from skeletal muscle following exercise. METHODS: We investigated the origin of exercise-induced ANGPTL4 in humans by measuring the arterial-to-venous difference over the leg and the hepato-splanchnic bed during an acute bout of exercise...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29017031/angiopoietin-like-4-is-a-wnt-signaling-antagonist-that-promotes-lrp6-turnover
#18
Nadine Kirsch, Ling-Shih Chang, Stefan Koch, Andrey Glinka, Christine Dolde, Gabriele Colozza, Maria D J Benitez, Edward M De Robertis, Christof Niehrs
Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6). This protein complex is internalized via clathrin-mediated endocytosis and degraded in lysosomes, leading to attenuation of Wnt/β-catenin signaling...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28984319/angiopoietin-like-3-in-lipoprotein-metabolism
#19
REVIEW
Sander Kersten
Triglycerides and cholesterol circulate in the bloodstream as part of various lipoprotein particles. Three members of the angiopoietin-like (ANGPTL) protein family - ANGPTL3, ANGPTL4 and ANGPTL8 - have emerged as important regulators of plasma lipoprotein levels by inhibiting the enzyme lipoprotein lipase. Here, I review the role of ANGPTL3 in lipoprotein metabolism. In contrast to ANGPTL4 and ANGPTL8, ANGPTL3 is exclusively produced in the liver and can therefore be classified as a true hepatokine. ANGPTL3 cooperates with ANGPTL8 to inhibit lipoprotein lipase and is mostly active after feeding, whereas ANGPTL4 is mostly active after fasting...
December 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28972886/paeoniflorin-ameliorates-adriamycin-induced-nephrotic-syndrome-through-the-ppar%C3%AE-angptl4-pathway-in-vivo-and-vitro
#20
Ruirui Lu, Jie Zhou, Bihao Liu, Ning Liang, Yu He, Lixia Bai, Peichun Zhang, Yanchun Zhong, Yuan Zhou, Jiuyao Zhou
Paeoniflorin (PF), an effective composition that is extracted from Radix Paeoniae Alba, plays a role in protecting against various kidney diseases. However, the mechanism of PF on nephrotic syndrome (NS) remains unclear. The aim of this study was to investigate the protective role of PF on Adriamycin (ADR)-induced NS in vivo and vitro as well as its potential mechanism. In animal study, PF significantly decreased the levels of 24-h urine protein, blood urea nitrogen, serum creatinine, total cholesterol and triglycerides in NS rats, but increased the total protein and albumin levels...
September 30, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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