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Ldl-receptor-related protein

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https://www.readbyqxmd.com/read/29773828/single-nucleotide-polymorphisms-in-the-g-protein-coupled-receptor-kinase-5-grk5-gene-are-associated-with-plasma-ldl-cholesterol-levels-in-humans
#1
Stefan Z Lutz, Mathias Falcenberg, Fausto Machicao, Andreas Peter, Martin Kächele, Elko Randrianarisoa, Angela Lehn-Stefan, Robert Wagner, Jürgen Machann, Fritz Schick, Martin Heni, Axel Ullrich, Andreas Fritsche, Norbert Stefan, Hans-Ulrich Häring, Harald Staiger, Konstantinos Kantartzis
Genetically modified mice models suggest an important role for G-protein-coupled receptor kinase 5 (GRK5) in the pathophysiology of obesity and related disorders. We investigated whether single nucleotide polymorphisms (SNPs) in the gene encoding GRK5 affect cardiometabolic traits in humans. We genotyped 3 common SNPs in intron 1 (rs1980030, rs10466210, rs9325562) and one SNP in intron 3 (rs10886471) of GRK5 in 2332 subjects at risk for type 2 diabetes. Total- and visceral fat mass were measured by magnetic resonance (MR) tomography and liver fat content by 1 H-MR spectroscopy...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29770231/cardiovascular-outcomes-of-pcsk9-inhibitors-with-special-emphasis-on-its-effect-beyond-ldl-cholesterol-lowering
#2
REVIEW
Dhrubajyoti Bandyopadhyay, Kumar Ashish, Adrija Hajra, Arshna Qureshi, Raktim K Ghosh
PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism. PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream. Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C...
2018: Journal of Lipids
https://www.readbyqxmd.com/read/29766560/further-options-for-treating-lipids-in-people-with-diabetes-targeting-ldl-cholesterol-and-beyond
#3
REVIEW
A S Wierzbicki
Diabetes is associated with increased cardiovascular disease (CVD) risk. Previous studies with statins have established that a 1 mmol/l reduction in LDL-cholesterol reduces CVD events by 21% over 5 years in people with diabetes. More recently, trials in people with acute coronary syndromes showed that ezetimibe reduced CVD events by 6% at 5 years and achieved a LDL-cholesterol of 1.6 mmol/l with better results in people with Type 2 diabetes. Several novel lipid-lowering therapies have recently been developed...
May 15, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29759006/interplay-between-hypercholesterolaemia-and-inflammation-in-atherosclerosis-translating-experimental-targets-into-clinical-practice
#4
José Tuñón, Magnus Bäck, Lina Badimón, Marie-Luce Bochaton-Piallat, Bertrand Cariou, Mat J Daemen, Jesus Egido, Paul C Evans, Sheila E Francis, Daniel Fj Ketelhuth, Esther Lutgens, Christian M Matter, Claudia Monaco, Sabine Steffens, Erik Stroes, Cécile Vindis, Christian Weber, Imo E Hoefer
Dyslipidaemia and inflammation are closely interconnected in their contribution to atherosclerosis. In fact, low-density lipoprotein (LDL)-lowering drugs have anti-inflammatory effects. The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) has shown that interleukin (IL)-1β blockade reduces the incidence of cardiovascular events in patients with previous myocardial infarction and C-reactive protein levels >2 mg/L. These data confirm the connection between lipids and inflammation, as lipids activate the Nod-like receptor protein 3 inflammasome that leads to IL-1β activation...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29755560/anti-hypercholesterolemic-effect-of-berbamine-isolated-from-rhizoma-coptidis-in-hypercholesterolemic-zebrafish-induced-by-high-cholesterol-diet
#5
Bing Han, Shuming Kou, Kai He, Yulong Han, Yue Wang, Tao Huang, Xia Zhou, Yubo Xiao, Xuegang Li, Xiaoli Ye
The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis (RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol (HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently labeled cholesterol in caudal artery was reduced dose-dependently after BBM treatment. For adult zebrafish, administration of 0.2% BBM exhibited a significant decrease in plasma total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) levels by 37%, 38% and 28%, respectively, along with a fall in lipid content in liver...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29749311/role-of-the-ldl-receptor-related-protein-1-in-regulating-protease-activity-and-signaling-pathways-in-the-vasculature
#6
Dianaly T Au, Allison L Arai, William E Fondrie, Selen C Muratoglu, Dudley K Strickland
Aortic aneurysms represent a significant clinical problem as they largely go undetected until a rupture occurs. Currently, an understanding of mechanisms leading to aneurysm formation is limited. Numerous studies clearly indicate that vascular smooth muscle cells play a major role in the development and response of the vasculature to hemodynamic changes and defects in these responses can lead to aneurysm formation. The LDL receptor-related protein 1 (LRP1) is major smooth muscle cell receptor that has the capacity to mediate the endocytosis of numerous ligands and to initiate and regulate signaling pathways...
May 11, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29736889/population-pharmacokinetics-and-exposure-response-modeling-and-simulation-for-evolocumab-in-healthy-volunteers-and-patients-with-hypercholesterolemia
#7
Mita Kuchimanchi, Anita Grover, Maurice G Emery, Ransi Somaratne, Scott M Wasserman, John P Gibbs, Sameer Doshi
Evolocumab, a novel human monoclonal antibody, inhibits proprotein convertase subtilisin/kexin type 9, a protein that targets low-density lipoprotein-cholesterol (LDL-C) receptors for the treatment of hyperlipidemia. The primary objective of this analysis was to characterize the population pharmacokinetics (popPK) and exposure-response relationship of evolocumab to assess if dose adjustment is needed across differing patient populations. Data were pooled for 5474 patients in 11 clinical studies who received evolocumab doses of 7-420 mg at various frequencies, either intravenously or subcutaneously...
May 7, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29713391/metabolic-and-inflammatory-biomarkers-are-associated-with-epigenetic-aging-acceleration-estimates-in-the-goldn-study
#8
Marguerite R Irvin, Stella Aslibekyan, Anh Do, Degui Zhi, Bertha Hidalgo, Steven A Claas, Vinodh Srinivasasainagendra, Steve Horvath, Hemant K Tiwari, Devin M Absher, Donna K Arnett
Background: Recently, epigenetic age acceleration-or older epigenetic age in comparison to chronological age-has been robustly associated with mortality and various morbidities. However, accelerated epigenetic aging has not been widely investigated in relation to inflammatory or metabolic markers, including postprandial lipids. Methods: We estimated measures of epigenetic age acceleration in 830 Caucasian participants from the Genetics Of Lipid Lowering Drugs and diet Network (GOLDN) considering two epigenetic age calculations based on differing sets of 5'-Cytosine-phosphate-guanine-3' genomic site, derived from the Horvath and Hannum DNA methylation age calculators, respectively...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29707570/whole-body-vibration-retards-progression-of-atherosclerosis-via-insulin-like-growth-factor-1-in-apolipoprotein-e-deficient-mice
#9
He Wu, Yibo Zhang, Xuan Yang, Xian Li, Zhenya Shao, Zipeng Zhou, Yuanlong Li, Shuwen Pan, Chang Liu
Whole body vibration (WBV) has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS). To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE-/- ) AS mice, which were trained by WBV (15 Hz, 30 min) for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R), interleukin 6 (IL-6), and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29703160/shp2-inhibitor-phps1-protects-against-atherosclerosis-by-inhibiting-smooth-muscle-cell-proliferation
#10
Jia Chen, Zhiyong Cao, Jingshu Guan
BACKGROUND: Smooth muscle cells play an important role in the development of atherosclerosis. SHP2 is known to regulate the proliferation and migration of smooth muscle cells. The purpose of this study was to determine whether the SHP2 inhibitor PHPS1 has a pro-atherosclerotic or an atheroprotective effect in vivo and in vitro. METHODS: After exposure to a high-cholesterol diet for 4 weeks, LDL receptor-deficient (Ldlr-/- ) mice were exposed to the SHP2 inhibitor PHPS1 or vehicle...
April 27, 2018: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29669912/insulin-induced-exocytosis-regulates-the-cell-surface-level-of-low-density-lipoprotein-related-protein-1-in-m%C3%A3-ller-glial-cells
#11
Virginia Actis Dato, Rubén A Grosso, María C Sánchez, Claudio M Fader, Gustavo A Chiabrando
Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) is expressed in retinal Müller glial cells (MGCs) and regulates intracellular translocation to the plasma membrane (PM) of the membrane proteins involved in cellular motility and activity. Different functions of MGCs may be influenced by insulin, including the removal of extracellular glutamate in the retina. In the present work, we investigated whether insulin promotes LRP1 translocation to the PM in the Müller glial-derived cell line MIO-M1...
April 18, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29602140/effect-of-simvastatin-and-ezetimibe-on-supar-levels-and-outcomes
#12
Gethin W Hodges, Casper N Bang, Julie L Forman, Michael H Olsen, Kurt Boman, Simon Ray, Y Antero Kesäniemi, Jesper Eugen-Olsen, Anders M Greve, Jørgen L Jeppesen, Kristian Wachtell
BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model...
March 16, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29571893/air-pollution-is-associated-with-the-development-of-atherosclerosis-via-the-cooperation-of-cd36-and-nlrp3-inflammasome-in-apoe-mice
#13
Xihao Du, Jiang Shuo, Xuejiao Zeng, Jia Zhang, Kun Pan, Ji Zhou, Yuquan Xie, Haidong Kan, Weimin Song, Qinghua Sun, Jinzhuo Zhao
Previous studies have indicated that the main air pollutant fine particulate matter (≤2.5 μm; PM2.5 ) exposure is associated with the development of atherosclerosis. Although the mechanism is not fully illustrated, the inflammatory responses play an important role. The present study aimed to explore whether PM2.5 -exacerbated atherosclerosis was mediated by the cooperation of cluster of differentiation 36 (CD36) and nucleotide-binding oligomerization domain-like receptor protein (NLRP3) inflammasome in apolipoprotein E-/- (ApoE-/- ) mice...
March 20, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29561321/an-update-on-trials-of-novel-lipid-lowering-drugs
#14
Anthony S Wierzbicki, Timothy M Reynolds, Adie Viljoen
PURPOSE OF REVIEW: A number of novel trials have assessed the efficacy of new lipid-lowering therapies in cardiovascular disease (CVD). RECENT FINDINGS: Proprotein convertase subtilisin kexin-9 inhibitors reduce low-density lipoprotein cholesterol (LDL-C) by 50-55%. A CVD outcome trial in patients with acute coronary syndromes with evolocumab achieved a LDL-C of 0.8 mmol/l (31 mg/dl) and a 20% relative risk reduction in CVD events in 2.2 years. Cholesterol ester transfer protein inhibitors raise high-density lipoprotein cholesterol and can lower LDL-C...
March 19, 2018: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/29559555/site-specific-o-glycosylation-of-members-of-the-low-density-lipoprotein-receptor-superfamily-enhances-ligand-interactions
#15
Shengjun Wang, Yang Mao, Yoshiki Narimatsu, Zilu Ye, Weihua Tian, Christoffer K Goth, Erandi Lira-Navarrete, Nis Borbye Pedersen, Asier Benito-Vicente, Cesar Martin, Kepa B Uribe, Ramon Hurtado-Guerrero, Christina Christoffersen, Nabil G Seidah, Rikke Nielsen, Erik I Christensen, Lars Hansen, Eric P Bennett, Sergey Y Vakhrushev, Katrine T Schjoldager, Henrik Clausen
The low-density lipoprotein receptor (LDLR) and related proteins are important for the transport of diverse biomolecules across cell membranes and barriers. Their functions are especially relevant for cholesterol homeostasis and diseases, including neurodegenerative and kidney disorders. Members of the LDLR-related protein family share LDLR class A (LA) repeats providing binding properties for lipoproteins and other biomolecules. We previously demonstrated that short linker regions between these LA repeats contain conserved O-glycan-sites...
March 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29556189/royal-jelly-reduces-cholesterol-levels-ameliorates-a%C3%AE-pathology-and-enhances-neuronal-metabolic-activities-in-a-rabbit-model-of-alzheimer-s-disease
#16
Yongming Pan, Jianqin Xu, Cheng Chen, Fangming Chen, Ping Jin, Keyan Zhu, Chenyue W Hu, Mengmeng You, Minli Chen, Fuliang Hu
Alzheimer's disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29551973/shexiang-baoxin-pill-corrects-metabolic-disorders-in-a-rat-model-of-metabolic-syndrome-by-targeting-mitochondria
#17
Dan Wei, Ningning Zheng, Lanyan Zheng, Leting Wang, Liang Song, Luning Sun
Background: Metabolic syndrome (MS) is a global epidemic that has great socioeconomic and public health implications. This study reports observed effects of the Shexiang Baoxin Pill (SBP) in a rat model of MS and explores its underlying mechanisms of action. Methods: A diet-induced rat model of MS was established according to accepted methods, and the rats were randomly divided into two groups: a control group (0.9% NaCl, 100 mg/kg• d) and a SBP-treated group (SBP, 100 mg/kg• d). Systolic blood pressures, fasting blood glucose (FBS) levels, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, body weights, and abdominal perimeters were dynamically monitored and analyzed...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29550924/role-of-lactoferrin-and-its-receptors-on-biliary-epithelium
#18
Romina Mancinelli, Francesca Olivero, Guido Carpino, Diletta Overi, Luigi Rosa, Maria Stefania Lepanto, Antimo Cutone, Antonio Franchitto, Gianfranco Alpini, Paolo Onori, Piera Valenti, Eugenio Gaudio
Human lactoferrin is an iron-binding glycoprotein present at high concentrations in breast milk and colostrum. It is produced by many exocrine glands and widely distributed in a variety of body fluids. This protein has antimicrobial, immunomodulatory, antioxidant, and anticancer properties. Two important hLf receptors have been identified: LDL receptor related protein (LRP1), a low specificity receptor, and intelectin-1 (ITLN1), a high specificity receptor. No data are present on the role of hLf on the biliary epithelium...
March 17, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29545368/commd-family-regulates-plasma-ldl-levels-and-attenuates-atherosclerosis-through-stabilizing-the-ccc-complex-in-endosomal-ldlr-trafficking
#19
Alina Fedoseienko, Melinde Wijers, Justina C Wolters, Daphne Dekker, Marieke Smit, Nicolette Huijkman, Niels Kloosterhuis, Helene Klug, Aloys Schepers, Ko Willems van Dijk, Johannes H Levels, Daniel D Billadeau, Marten H Hofker, Jan van Deursen, Marit Westerterp, Ezra Burstein, Jan Albert Kuivenhoven, Bart van de Sluis
<u>Rationale:</u> <u>CO</u> pper<u>M</u>etabolism<u>M</u>URR1 Domain-containing (COMMD) proteins are a part of the COMMD-CCDC22-CCDC93 (CCC) complexes facilitating endosomal trafficking of cell surface receptors. Hepatic COMMD1 inactivation decreases CCDC22 and CCDC93 protein levels, impairs the recycling of the low-density lipoprotein receptor (LDLR), and increases plasma LDL cholesterol levels in mice. However, whether any of the other COMMD members function similarly as COMMD1, and whether perturbation in the CCC complex promotes atherogenesis remain unclear...
March 15, 2018: Circulation Research
https://www.readbyqxmd.com/read/29545257/advanced-whole-genome-sequencing-and-analysis-of-fetal-genomes-from-amniotic-fluid
#20
Qing Mao, Robert Chin, Weiwei Xie, Yuqing Deng, Wenwei Zhang, Huixin Xu, Rebecca Yu Zhang, Quan Shi, Erin E Peters, Natali Gulbahce, Zhenyu Li, Fang Chen, Radoje Drmanac, Brock A Peters
BACKGROUND: Amniocentesis is a common procedure, the primary purpose of which is to collect cells from the fetus to allow testing for abnormal chromosomes, altered chromosomal copy number, or a small number of genes that have small single- to multibase defects. Here we demonstrate the feasibility of generating an accurate whole-genome sequence of a fetus from either the cellular or cell-free DNA (cfDNA) of an amniotic sample. METHODS: cfDNA and DNA isolated from the cell pellet of 31 amniocenteses were sequenced to approximately 50× genome coverage by use of the Complete Genomics nanoarray platform...
March 15, 2018: Clinical Chemistry
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