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Ldl-receptor-related protein

Nathália Grave, Luciana Tovo-Rodrigues, Janaína da Silveira, Diego Luiz Rovaris, Simone Morelo Dal Bosco, Verônica Contini, Júlia Pasqualini Genro
Much evidence suggests an association between vitamin D deficiency and chronic diseases such as obesity and dyslipidemia. Although genetic factors play an important role in the etiology of these diseases, only a few studies have investigated the relationship between vitamin D-related genes and anthropometric and lipid profiles. The aim of this study was to investigate the association of three vitamin D-related genes with anthropometric and lipid parameters in 542 adult individuals. We analyzed the rs2228570 polymorphism in the vitamin D receptor gene (VDR), rs2134095 in the retinoid X receptor gamma gene (RXRG) and rs7041 in the vitamin D-binding protein gene (GC)...
August 15, 2016: Journal of Nutritional Biochemistry
Mengsi Hu, Minghua Fan, Junhui Zhen, Jiangong Lin, Qun Wang, Zhimei Lv, Rong Wang
Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that regulates cell adhesion, proliferation and differentiation. In the present study, a rat model of high fat diet-induced hypercholesterolaemia was established to investigate the involvement of FAK in lipid disorder-related kidney diseases. We showed focal fusion of podocyte foot process that occurred at as early as 4 weeks in rats consuming high fat diet, preceding the onset of proteinuria when aberrant phosphorylation of FAK was found...
October 5, 2016: Journal of Cellular and Molecular Medicine
Julie Leca, Sébastien Martinez, Sophie Lac, Jérémy Nigri, Véronique Secq, Marion Rubis, Christian Bressy, Arnauld Sergé, Marie-Noelle Lavaut, Nelson Dusetti, Céline Loncle, Julie Roques, Daniel Pietrasz, Corinne Bousquet, Stéphane Garcia, Samuel Granjeaud, Mehdi Ouaissi, Jean Baptiste Bachet, Christine Brun, Juan L Iovanna, Pascale Zimmermann, Sophie Vasseur, Richard Tomasini
The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk...
October 4, 2016: Journal of Clinical Investigation
Biying Huang, Per Svensson, Johan Ärnlöv, Johan Sundström, Lars Lind, Erik Ingelsson
BACKGROUND AND AIMS: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years)...
September 15, 2016: Atherosclerosis
Rafael Escate, Teresa Padro, Maria Borrell-Pages, Rosa Suades, Rosa Aledo, Pedro Mata, Lina Badimon
Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL...
September 29, 2016: Journal of Cellular and Molecular Medicine
Michael G Silverman, Brian A Ference, Kyungah Im, Stephen D Wiviott, Robert P Giugliano, Scott M Grundy, Eugene Braunwald, Marc S Sabatine
IMPORTANCE: The comparative clinical benefit of nonstatin therapies that reduce low-density lipoprotein cholesterol (LDL-C) remains uncertain. OBJECTIVE: To evaluate the association between lowering LDL-C and relative cardiovascular risk reduction across different statin and nonstatin therapies. DATA SOURCES AND STUDY SELECTION: The MEDLINE and EMBASE databases were searched (1966-July 2016). The key inclusion criteria were that the study was a randomized clinical trial and the reported clinical outcomes included myocardial infarction (MI)...
September 27, 2016: JAMA: the Journal of the American Medical Association
Yanyong Xu, Hongmei Liu, Mengting Liu, Feifei Li, Liangchen Liu, Fen Du, Daping Fan, Hong Yu
Apolipoprotein E (apoE) is well known as an antiatherogenic protein via regulating lipid metabolism and inflammation. We previously reported that a human apoE mimetic peptide, EpK, reduced atherosclerosis in apoE null (apoE(-/-)) mice through reducing inflammation without affecting plasma lipid levels. Here, we construct another human apoE mimetic peptide, named hEp, and investigate whether expression of hEp can reduce atherosclerotic lesion development in aged female apoE(-/-) mice with pre-existing lesions...
2016: American Journal of Translational Research
Elaine N Daminelli, Ana E M Martinelli, Adriana Bulgarelli, Fatima R Freitas, Raul C Maranhão
PURPOSE: After injection in the bloodstream, a lipid nanoparticle (LDE) resembling low-density lipoprotein (LDL) concentrates in atherosclerotic lesions of cholesterol-fed rabbits. Here, rabbits with atherosclerosis were treated with carmustine, an antiproliferative agent used in cancer chemotherapy, associated to LDE to investigate the effects on the lesions. METHODS: Twenty-seven male New Zealand rabbits were fed a 1 % cholesterol diet for 8 weeks. After 4 weeks nine animals were treated with intravenous saline solution, nine with intravenous LDE alone, and nine with intravenous LDE-carmustine (4 mg/kg, weekly for 4 weeks)...
October 2016: Cardiovascular Drugs and Therapy
Arno G Beer, Christoph Zenzmaier, Michael Schreinlechner, Jenny Haas, Martin F Dietrich, Joachim Herz, Peter Marschang
Low-density lipoprotein (LDL) receptor-related protein 1B (LRP1B), a member of the LDL receptor family, is frequently inactivated in multiple malignancies including lung cancer. LRP1B is therefore considered as a putative tumor suppressor. Due to its large size (4599 amino acids), until now only minireceptors or receptor fragments have been successfully cloned. To assess the effect of LRP1B on the proliferation of non-small cell lung cancer cells, we constructed and expressed a transfection vector containing the 13...
September 8, 2016: Oncotarget
Gopalan Gnanaguru, Ariel R Choi, Dhanesh Amarnani, Patricia A D'Amore
PURPOSE: Accumulation of oxidized phospholipids/lipoproteins with age is suggested to contribute to the pathogenesis of AMD. We investigated the effect of oxidized LDL (ox-LDL) on human RPE cells. METHODS: Primary human fetal RPE (hf-RPE) and ARPE-19 cells were treated with different doses of LDL or ox-LDL. Assessment of cell death was measured by lactate dehydrogenase release into the conditioned media. Barrier function of RPE was assayed by measuring transepithelial resistance...
September 1, 2016: Investigative Ophthalmology & Visual Science
Thomas Grenkowitz, Ursula Kassner, Marion Wühle-Demuth, Bastian Salewsky, Adrian Rosada, Tomasz Zemojtel, Werner Hopfenmüller, Berend Isermann, Katrin Borucki, Franz Heigl, Ulrich Laufs, Stephan Wagner, Marcus E Kleber, Priska Binner, Winfried März, Elisabeth Steinhagen-Thiessen, Ilja Demuth
BACKGROUND AND AIMS: Autosomal-dominant familial hypercholesterolemia (FH) is characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and a dramatically increased risk to develop cardiovascular disease (CVD). Mutations in three major genes have been associated with FH: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB), and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). Here we investigated the frequency and the spectrum of FH causing mutations in Germany...
October 2016: Atherosclerosis
Emilia Laudati, Andrew S Gilder, Michael S Lam, Roberta Misasi, Maurizio Sorice, Steven L Gonias, Elisabetta Mantuano
LDL Receptor-related Protein-1 (LRP1) is an endocytic receptor for diverse ligands. In neurons and neuron-like cells, ligand-binding to LRP1 initiates cell-signaling. Herein, we show that in PC12 and N2a neuron-like cells, LRP1 distributes into lipid rafts and non-raft plasma membrane fractions. When lipid rafts were disrupted, using methyl-β-cyclodextrin or fumonisin B1, activation of Src family kinases and ERK1/2 by the LRP1 ligands, tissue-type plasminogen activator and activated α2-macroglobulin, was blocked...
October 2016: Molecular and Cellular Neurosciences
Colin W Garvie, Cara V Fraley, Nadine H Elowe, Elizabeth K Culyba, Christopher T Lemke, Brian K Hubbard, Virendar K Kaushik, Douglas S Daniels
Circulating low-density lipoprotein cholesterol (LDLc) is regulated by membrane-bound LDL receptor (LDLr). Upon LDLc and LDLr interaction the complex is internalized by the cell, leading to LDLc degradation and LDLr recycling back to the cell surface. The proprotein convertase subtilisin/kexin type 9 (PCSK9) protein regulates this cycling. PCSK9 is secreted from the cell and binds LDLr. When the complex is internalized, PCSK9 prevents LDLr from shuttling back to the surface and instead targets it for degradation...
August 18, 2016: Protein Science: a Publication of the Protein Society
Tixieanna Dissmore, Cheikh I Seye, Denis M Medeiros, Gary A Weisman, Barry Bardford, Laman Mamedova
BACKGROUND AND AIMS: The internalization of aggregated low-density lipoproteins (agLDL) mediated by low-density lipoprotein receptor related protein (LRP1) may involve the actin cytoskeleton in ways that differ from the endocytosis of soluble LDL by the LDL receptor (LDLR). This study aims to define novel mechanisms of agLDL uptake through modulation of the actin cytoskeleton, to identify molecular targets involved in foam cell formation in vascular smooth muscle cells (VSMCs). The critical observation that formed the basis for these studies is that under pathophysiological conditions, nucleotide release from blood-derived and vascular cells activates SMC P2Y2 receptors (P2Y2Rs) leading to rearrangement of the actin cytoskeleton and cell motility...
September 2016: Atherosclerosis
Youngmin Kim, Mi-Jin Kwon, Jeong-Wook Choi, Min-Kyeong Lee, Chorong Kim, Jaehun Jung, Heny Aprianita, Heesop Nam, Taek-Jeong Nam
The aim of this study was to examine the anti-obesity effects of boiled tuna extract in C57BL/6N mice with obesity induced by a high-fat diet (HFD). We determined the anti-obesity effects of boiled tuna extract (100, 200, or 400 mg/kg) on the progression of HFD-induced obesity for 10 weeks. The mice were divided into 5 groups as follows: the normal diet (ND) group (n=10); the HFD group (n=10); the mice fed HFD and 100 mg/kg boiled tuna extract group (n=10); those fed a HFD and 200 mg/kg boiled tuna extract group (n=10); and those fed a HFD and 400 mg/kg boiled tuna extract group (n=10)...
October 2016: International Journal of Molecular Medicine
Jane Palsgaard, Brice Emanuelli, Jonathon N Winnay, Grzegorz Sumara, Gerard Karsenty, C Ronald Kahn
No abstract text is available yet for this article.
August 5, 2016: Journal of Biological Chemistry
Juristo Fonolla-Joya, Rebeca Reyes-García, Antonia García-Martín, Eduardo López-Huertas, Manuel Muñoz-Torres
OBJECTIVE: Nutritional strategies can be effective for the prevention of menopause-related diseases, such as osteoporosis and cardiovascular disease. Our aim was to evaluate the effects of a dairy product enriched in polyunsaturated fatty acids, calcium, oleic acid, and vitamins on cardiovascular markers and bone metabolism in postmenopausal women with moderate cardiovascular risk. METHODS: One hundred seventeen healthy postmenopausal women (aged 45 ± 7.7 years) were allocated to 2 groups: the intervention group (IG; n = 63), who consumed 0...
August 2016: Journal of the American College of Nutrition
Jian Guo, Yang Li, Yi-Hong Ren, Zhijun Sun, Jie Dong, Han Yan, Yujun Xu, Dao Wen Wang, Gu-Yan Zheng, Jie Du, Xiao-Li Tian
Mutations in the genes low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) and myocyte enhancer factor 2A (MEF2A) were reported in families with coronary artery disease (CAD). We intend to determine the mutational spectrum of these genes among hyperlipidemic and normolipidemic CAD families. Forty probands with early-onset CAD were recruited from 19 hyperlipidemic and 21 normolipidemic Chinese families. We sequenced all exons and intron-exon boundaries of LRP6 and MEF2A, and found a novel heterozygous variant in LRP6 from a proband with normolipidemic CAD...
2016: International Journal of Molecular Sciences
Kamel Boukais, Richard Bayles, Luciano de Figueiredo Borges, Liliane Louedec, Yacine Boulaftali, Benoit Ho-Tin-Noé, Véronique Arocas, Marie-Christine Bouton, Jean-Baptiste Michel
Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin...
2016: Frontiers in Physiology
Ahamed Hossain, Lamiya Tauhid, Ian Davenport, Thomas Huckaba, Richard Graves, Tarun Mandal, Syed Muniruzzaman, Syed A Ahmed, Partha S Bhattacharjee
PURPOSE: The cell surface LDL (low-density lipoprotein) receptor-related protein-1 (LRP-1) is important for lipid transport and several cell signaling processes. Human apolipoprotein E (apoE) is a ligand of LRP-1. We previously reported that a short peptide (apoEdp) mimicking the LRP-1 binding region of apoE prevents hyperglycemia-induced retinal endothelial cell dysfunction in vitro. The in-vivo outcome of apoE-based peptidomimetic inhibition of LRP-1 in the treatment of diabetic retinopathy is unknown...
July 21, 2016: Current Eye Research
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