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Mohamed Abu-Farha, Irina Al-Khairi, Preethi Cherian, Betty Chandy, Devarajan Sriraman, Asma Alhubail, Faisal Al-Refaei, Abdulmohsen AlTerki, Jehad Abubaker
BACKGROUND: Hypertriglyceridemia is associated with increased risk for cardiovascular diseases and type 2 diabetes (T2D). Angiopoietin like proteins particularly 3, 4 and recently 8 are well established regulators of plasma triglyceride level through regulating the activity of lipoprotein lipase. Plasma level and association between ANGPTL3, 4 and 8 is not well established in human subjects. This study was designed to establish the level of these proteins in plasma and adipose tissues and investigate the association between ANGPTL8 with ANGPTL3 and 4 in T2D and non-diabetics subjects...
October 13, 2016: Lipids in Health and Disease
Christian Klingler, Xinjie Zhao, Till Adhikary, Jia Li, Guowang Xu, Hans-Ulrich Häring, Erwin Schleicher, Rainer Lehmann, Cora Weigert
Metabolomics studies of human plasma demonstrate a correlation of lower plasma lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity, and inflammation. This relationship is not unraveled on a molecular level. Here we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human myotubes treated with 10μM LPC for 24h revealed enrichment of up-regulated peroxisome proliferator-activated receptor (PPAR) target transcripts, including ANGPTL4, PDK4, PLIN2, and CPT1A...
September 30, 2016: Biochimica et Biophysica Acta
Ahmed Saad, Xiang-Yang Zhu, Sandra Herrmann, LaTonya Hickson, Hui Tang, Allan B Dietz, Andre J van Wijnen, Lilach Lerman, Stephen Textor
BACKGROUND: Adipose-derived MSC (AMSCs) possess angiogenic and immunomodulatory properties that may modulate kidney regeneration. Whether these properties are retained in older patients with atherosclerotic vascular disease is poorly understood. Hypoxic conditions are known to modify properties and growth characteristics of AMSCs. We tested the hypothesis that AMSCs from older patients with atherosclerotic renovascular disease (RVD) differ from normal kidney donors, and whether hypoxia changes their functional and molecular properties to promote angiogenesis...
2016: Stem Cell Research & Therapy
Elisa Gomez Perdiguero, Athanasia Liabotis-Fontugne, Mélanie Durand, Clément Faye, Sylvie Ricard-Blum, Manuel Simonutti, Sébastien Augustin, Bryan M Robb, Michel Paques, David M Valenzuela, Andrew J Murphy, George D Yancopoulos, Gavin Thurston, Ariane Galaup, Catherine Monnot, Stéphane Germain
Dynamic control of endothelial cell junctions is essential for vascular homeostasis and angiogenesis. We recently provided genetic evidence that ANGPTL4 is a key regulator of vascular integrity both during developmental and in hypoxia-induced pathological conditions. The purpose of the present study was to decipher the molecular mechanisms through which ANGPTL4 regulates vascular integrity. Using surface plasmon resonance and proximity ligation assays, we show that ANGPTL4 binds integrin αvβ3. In vitro and in vivo functional assays with Angptl4-deficient mice demonstrate that ANGPTL4-αvβ3 interaction is necessary to mediate ANGPTL4 vasoprotective effects...
August 31, 2016: Journal of Pathology
Yi Wang, Li-Ming Liu, Li Wei, Wei-Wei Ye, Xiang-Ying Meng, Feng Chen, Qian Xiao, Jian-Yang Chen, Yong Zhou
Angiopoietin-like protein 4 (Angptl4) is a secreted protein predominantly expressed in liver and adipose tissues, and has been identified as an adipokine. Angptl4 is the target gene of peroxisome proliferator‑activated receptors, which are widely used as lipid‑lowering and anti‑diabetic drugs, and previous studies have demonstrated that Angptl4 is able to directly stimulate adipocyte lipolysis. The current study focused on how Angptl4 was involved in regulating lipid and glucose metabolism in high‑fat‑diet (HFD) C57 mice...
October 2016: Molecular Medicine Reports
Julia Dotterweich, Katrin Schlegelmilch, Alexander Keller, Beate Geyer, Doris Schneider, Sabine Zeck, Robert J J Tower, Regina Ebert, Franz Jakob, Norbert Schütze
Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6...
August 9, 2016: Bone
Takuya Tanaka, Takahisa Imamura, Masakazu Yoneda, Atsushi Irie, Hidenao Ogi, Masashi Nagata, Ryoji Yoshida, Daiki Fukuma, Kenta Kawahara, Masanori Shinohara, Hideki Nakayama
To study the role of TNF-α in tongue cancer metastasis, we made highly metastatic cells from a human oral squamous cell carcinoma cell line (SAS) by repeating the passage in which the cells were injected into a nude mouse tongue and harvested from metastasized cervical lymph nodes. Cancer cells after 5 passages (GSAS/N5) increased invasive activity 7-fold in a TNF-α receptor 1 (TNFR1)-dependent manner and enhanced mRNA expression of TNF-α and TNFR1. In the highly metastatic cells, NF-κB activation was upregulated via elevated phosphorylation of Akt and Ikkα/β in the signaling pathway and secretion of TNF-α, active MMP-2 and MMP-9 increased...
October 2016: International Journal of Oncology
Zhiquan Huang, Jiemin Xie, Shiyao Lin, Shihao Li, Zixian Huang, Youyuan Wang, Jiantao Ye
OBJECTIVE: Tongue squamous cell carcinoma (TSCC) is the most common malignant cancer in the oral cavity, with a high rate of metastasis to the neck lymphoid node. Angiopoietin-like protein 4 (ANGPTL4) and microvessel density (MVD) may be novel indicators for tumor metastasis. The aim of the present study was to investigate the expression and function of ANGPTL4 in TSCC and the relationship between ANGPTL4 and MVD. METHODS: The expression levels of ANGPTL4 and MVD (CD34) were analyzed in 65 TSCC specimens and the adjacent non-cancerous tissues using immunohistochemistry (IHC)...
November 2016: Archives of Oral Biology
Binod Aryal, Noemi Rotllan, Elisa Araldi, Cristina M Ramírez, Shun He, Benjamin G Chousterman, Ashley M Fenn, Amarylis Wanschel, Julio Madrigal-Matute, Nikhil Warrier, Jose L Martín-Ventura, Filip K Swirski, Yajaira Suárez, Carlos Fernández-Hernando
Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population...
2016: Nature Communications
Lionel Clément, Camille Macé
Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria...
June 2016: Médecine Sciences: M/S
Pengfei Li, Nan Sun, Jianchun Zeng, Yirong Zeng, Yueguang Fan, Wenjun Feng, Jie Li
BACKGROUND: Apoptosis of osteoblasts and osteocytes is one cause of steroid-induced osteonecrosis of the femoral head; however, the molecular mechanism of steroid affecting osteoblasts at the genetic level is unclear. The aim of the present work is to examine differential expression of osteoblasts in rats after steroid intervention and to verify expression by real-time polymerase chain reaction (RT-PCR). METHODS: Primary culture, passaging and identification of osteoblasts of SD neonatal rats were conducted; osteoblasts were divided into two groups, the control group, and the steroid group...
October 10, 2016: Gene
Nishika Sahini, Jürgen Borlak
Nonalcoholic fatty liver disease (NAFLD) is a common disorder hallmarked by excessive lipid deposits. Based on our recent research on lipid droplet (LD) formation in hepatocytes, we investigated LD-associated gene regulations in NAFLD of different grades, that is, steatosis vs steatohepatitis by comparing liver biopsies from healthy controls (N = 13) and NAFLD patients (N = 102). On average, more than 700 differentially expressed genes (DEGs) were identified of which 146 are mechanistically linked to LD formation...
June 16, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Wenyu Wang, Yang Liu, Jingcan Hao, Shuyu Zheng, Yan Wen, Xiao Xiao, Awen He, Qianrui Fan, Feng Zhang, Ruiyu Liu
Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8)...
October 10, 2016: Gene
Marie K Kirby, Ryne C Ramaker, Jason Gertz, Nicholas S Davis, Bobbi E Johnston, Patsy G Oliver, Katherine C Sexton, Edward W Greeno, John D Christein, Martin J Heslin, James A Posey, William E Grizzle, Selwyn M Vickers, Donald J Buchsbaum, Sara J Cooper, Richard M Myers
BACKGROUND: Pancreatic adenocarcinoma patients have low survival rates due to late-stage diagnosis and high rates of cancer recurrence even after surgical resection. It is important to understand the molecular characteristics associated with survival differences in pancreatic adenocarcinoma tumors that may inform patient care. RESULTS: RNA sequencing was performed for 51 patient tumor tissues extracted from patients undergoing surgical resection, and expression was associated with overall survival time from diagnosis...
October 2016: Molecular Oncology
Maija Suvanto, Timo Jahnukainen, Marjo Kestilä, Hannu Jalanko
Polymorphic variants in several molecules involved in the glomerular function and drug metabolism have been implicated in the pathophysiology of pediatric idiopathic nephrotic syndrome (INS), but the results remain inconsistent. We analyzed the association of eleven allelic variants in eight genes (angiopoietin-like 4 (ANGPTL4), glypican 5 (GPC5), interleukin-13 (IL-13), macrophage migration inhibitory factor (MIF), neural nitric oxide synthetase (nNOS), multidrug resistance-1 (MDR1), glucocorticoid-induced transcript-1 (GLCCI1), and nuclear receptor subfamily-3 (NR3C1)) in 100 INS patients followed up till adulthood...
2016: International Journal of Nephrology
Andreas Leiherer, Kathrin Stoemmer, Axel Muendlein, Christoph H Saely, Elena Kinz, Eva M Brandtner, Peter Fraunberger, Heinz Drexel
Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases...
2016: Nutrients
(no author information available yet)
No abstract text is available yet for this article.
May 12, 2016: New England Journal of Medicine
Xiaoming Zhu, Xiaobin Guo, Sen Wu, Li Wei
Purpose Lung cancer remains the leading cause of cancer deaths with intricate mechanisms. In the present study, we evaluated the clinical significance and biological role of ANGPTL4 in non-small cell lung cancer (NSCLC), the most common lung cancer subtype. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for examining the mRNA level of ANGPTL4 in NSCLC tissues and adjacent non-tumor tissues, NSCLC cell lines, and the immortalized human bronchial epithelial cell line HBE, respectively...
August 2016: Lung
Caroline E Gargett, Shanti Gurung
No abstract text is available yet for this article.
June 2016: Biology of Reproduction
Anna Helgadottir, Solveig Gretarsdottir, Gudmar Thorleifsson, Eirikur Hjartarson, Asgeir Sigurdsson, Audur Magnusdottir, Aslaug Jonasdottir, Helgi Kristjansson, Patrick Sulem, Asmundur Oddsson, Gardar Sveinbjornsson, Valgerdur Steinthorsdottir, Thorunn Rafnar, Gisli Masson, Ingileif Jonsdottir, Isleifur Olafsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Maryam S Daneshpour, Davood Khalili, Fereidoun Azizi, Dorine W Swinkels, Lambertus Kiemeney, Arshed A Quyyumi, Allan I Levey, Riyaz S Patel, Salim S Hayek, Ingibjorg J Gudmundsdottir, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari Stefansson
Sequence variants affecting blood lipids and coronary artery disease (CAD) may enhance understanding of the atherogenicity of lipid fractions. Using a large resource of whole-genome sequence data, we examined rare and low-frequency variants for association with non-HDL cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in up to 119,146 Icelanders. We discovered 13 variants with large effects (within ANGPTL3, APOB, ABCA1, NR1H3, APOA1, LIPC, CETP, LDLR, and APOC1) and replicated 14 variants. Five variants within PCSK9, APOA1, ANGPTL4, and LDLR associate with CAD (33,090 cases and 236,254 controls)...
June 2016: Nature Genetics
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