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Ldl-receptor-related protein

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https://www.readbyqxmd.com/read/29157263/ldl-receptor-blockade-reduces-mortality-in-a-mouse-model-of-ischaemic-stroke-without-improving-tissue-type-plasminogen-activator-induced-brain-haemorrhage-towards-pre-clinical-simulation-of-symptomatic-ich
#1
Be'eri Niego, Brad R S Broughton, Heidi Ho, Christopher G Sobey, Robert L Medcalf
BACKGROUND: Symptomatic intracerebral haemorrhage (sICH) following tissue-type plasminogen activator (rt-PA) administration is the most feared and lethal complication of thrombolytic therapy for ischaemic stroke, creating a significant obstacle for a broader uptake of this beneficial treatment. rt-PA also undermines cerebral vasculature stability in a multimodal process which involves engagement with LDL receptor-related protein 1 (LRP-1), potentially underlying the development of sICH...
November 21, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29149696/clearance-of-plasmin-pn-1-complexes-by-vascular-smooth-muscle-cells-in-human-aneurysm-of-the-ascending-aorta
#2
Kamel Boukais, Luciano F Borges, Laurence Venisse, Ziad Touat, Déborah François, Véronique Arocas, Guillaume Jondeau, Paul Declerck, Marie-Christine Bouton, Jean-Baptiste Michel
Plasminogen is a circulating zymogen which enters the arterial wall by radial, transmural hydraulic conductance, where it is converted to plasmin by tissue plasminogen activator t-PA on an activation platform involving S100A4 on the vascular smooth muscle cell (vSMC) membrane. Plasmin is involved in the progression of human thoracic aneurysm of the ascending aorta (TAA). vSMCs protect the TAA wall from plasmin-induced proteolytic injury by expressing high levels of antiproteases. Protease nexin-1 (PN-1) is a tissue antiprotease belonging to the serpin superfamily, expressed in the vascular wall, and is able to form a covalent complex with plasmin...
October 24, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29144234/lrp1-integrates-murine-macrophage-cholesterol-homeostasis-and-inflammatory-responses-in-atherosclerosis
#3
Xunde Xian, Yinyuan Ding, Marco Dieckmann, Li Zhou, Florian Plattner, Mingxia Liu, John S Parks, Robert E Hammer, Philippe Boucher, Shirling Tsai, Joachim Herz
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGFβ and PDGFRβ in reverse cholesterol transport and the maintenance of vascular wall integrity...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29115480/protective-effects-of-probucol-on-ox-ldl-induced-epithelial-mesenchymal-transition-in-human-renal-proximal-tubular-epithelial-cells-via-lox%C3%A2-1-ros-mapk-signaling
#4
Bing Bing Zhu, Hao Wang, Yang Feng Chi, Yun Man Wang, Xing Mei Yao, Shuang Liu, Huiling Qiu, Ji Fang, Pei Hao Yin, Xue Mei Zhang, Wen Peng
Oxidized low-density lipoprotein (Ox-LDL), as a strong oxidant, results in renal injury through multiple mechanisms. The aim of the present study was to determine the injury effects of Ox‑LDL and the potential protective effects of the antioxidant reagent probucol on epithelial‑mesenchymal transition (EMT) in human renal proximal tubular epithelial cells (HK‑2) and to further explore the role and interrelation of lectin‑like oxidized low‑density lipoprotein receptor‑1 (LOX‑1), reactive oxygen species (ROS) and mitogen‑activated protein kinase (MAPK) pathway...
November 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113088/oxidative-stress-in-cardiovascular-diseases-involvement-of-nrf2-antioxidant-redox-signaling-in-macrophage-foam-cells-formation
#5
REVIEW
Bee Kee Ooi, Bey Hing Goh, Wei Hsum Yap
Oxidative stress is an important risk factor contributing to the pathogenesis of cardiovascular diseases. Oxidative stress that results from excessive reactive oxygen species (ROS) production accounts for impaired endothelial function, a process which promotes atherosclerotic lesion or fatty streaks formation (foam cells). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in cellular redox homeostasis. Upon exposure to oxidative stress, Nrf2 is dissociated from its inhibitor Keap-1 and translocated into the nucleus, where it results in the transcriptional activation of cell defense genes...
November 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29109760/influence-of-serum-hmw-adiponectin-level-in-patients-with-pregnancy-induced-hypertension-syndrome-on-the-occurrence-of-eclampsia-in-secondary-pregnancy
#6
Qian Xu, Dongmei Fan, Fahong Li, Zhanhong Zhang
In the present study, we studied the influence of serum high-molecular weight adiponectin (HMWA) levels in patients with pregnancy-induced hypertension (PIH) on the occurrence of eclampsia in secondary pregnancy and its related mechanisms. In total, 130 patients who were diagnosed with PIH for the first time were selected for this study; the median interval of the secondary pregnancy was 28.5 months. The serum HMWA and leptin levels both times were detected, and the insulin resistance indexes (HOMA-IR) were calculated...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29092018/the-function-of-hdl-and-ldl-in-the-maintenance-of-mouse-ovarian-steroid-balance
#7
Xin-Lian Chang, Lisheng Liu, Naiqiang Wang, Zi-Jiang Chen, Cong Zhang
The membrane proteins, low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SR-BI, gene name Scarb1), are lipoprotein receptors that play central roles in lipoprotein metabolism. Cholesterol bound in high-density lipoprotein (HDL) and LDL is transported into cells mainly by SR-BI and LDLR. The relative contribution of LDL and HDL to the steroidogenic cholesterol pool varies among species and may vary among tissues within one species. To investigate which of these pathways is more important in the supply of cholesterol in mouse ovary, we utilized immunohistochemistry, western blotting, RNAi and RT-PCR as well as Ldlr-/- mice to explore the uptake of HDL and LDL in the ovary...
October 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29074737/ldl-receptor-related-protein-2-megalin-as-a-target-antigen-in-human-kidney-anti-brush-border-antibody-disease
#8
Christopher P Larsen, Claire Trivin-Avillach, Paige Coles, A Bernard Collins, Michael Merchant, Hong Ma, Daniel W Wilkey, Josephine M Ambruzs, Nidia C Messias, L Nicholas Cossey, Ivy A Rosales, Thomas Wooldridge, Patrick D Walker, Robert B Colvin, Jon Klein, David J Salant, Laurence H Beck
Primary renal tubulointerstitial disease resulting from proximal tubule antigen-specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border...
October 26, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29073573/exposure-to-traffic-generated-air-pollutants-mediates-alterations-in-brain-microvascular-integrity-in-wildtype-mice-on-a-high-fat-diet
#9
Usa Suwannasual, JoAnn Lucero, Jacob D McDonald, Amie K Lund
Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs...
October 23, 2017: Environmental Research
https://www.readbyqxmd.com/read/29032149/tg-haplotype-in-the-lrp8-is-associated-with-myocardial-infarction-in-south-indian-population
#10
Muhammed Asif, Shivarama Bhat, Sheikh Nizamuddin, Mohammed S Mustak
Myocardial infarction (MI) is a complex multifactorial cardiovascular disease. India experiences a much greater burden of MI, also suggesting an experimental increase of this burden in the future. The absolute reasons for MI are context dependent and differ with different geographical settings. Several reports indicate that SNPs that are associated with certain diseases in other populations may not be associated with Indian population. It is, therefore, important to validate the association of SNPs. Low density lipoprotein receptor related protein 8 (LRP8) gene plays central role in human lipoprotein metabolism as it facilitates the clearance of bad cholesterol LDL, VLDL from plasma and is reported to be associated with MI in the western population...
October 12, 2017: Gene
https://www.readbyqxmd.com/read/29028997/serum-quantitative-proteomic-analysis-reveals-soluble-egfr-to-be-a-marker-of-insulin-resistance-in-male-mice-and-humans
#11
Mayu Kyohara, Jun Shirakawa, Tomoko Okuyama, Ayuko Kimura, Yu Togashi, Kazuki Tajima, Hisashi Hirano, Yasuo Terauchi
To identify circulating factors as candidates involved in type 2 diabetes (T2DM), we conducted two different quantitative proteomic analyses: 1) db/db mouse sera were compared with db/+ mouse sera obtained at 4, 8, 12, and 24 weeks of age, and 2) db/db mouse sera from animals treated with liraglutide were compared with sera from animals without liraglutide treatment. 20 and eight proteins were differentially expressed in db/db mouse sera in the first experiment and in db/db mouse sera after liraglutide treatment in the second experiment, respectively...
October 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/29028290/plasminogen-activator-inhibitor-1-regulates-the-vascular-expression-of-vitronectin
#12
M Luo, Y Ji, Y Luo, R Li, W P Fay, J Wu
Essentials Vitronectin (VN) is produced by smooth muscle cells (SMCs) and promotes neointima formation. We studied the regulation of vascular VN expression by plasminogen activator inhibitor-1 (PAI-1). PAI-1 stimulates VN gene expression in SMCs by binding LDL receptor-related protein 1. Stimulation of VN gene expression may be a mechanism by which PAI-1 controls vascular remodeling. SUMMARY: Background Increased expression of vitronectin (VN) by smooth muscle cells (SMCs) promotes neointima formation after vascular injury, and may contribute to chronic vascular diseases, such as atherosclerosis...
October 13, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29024318/antiphospholipid-antibody-induced-cellular-responses-depend-on-epitope-specificity-implications-for-treatment-of-antiphospholipid-syndrome
#13
N Müller-Calleja, A Hollerbach, F Häuser, A Canisius, C Orning, K J Lackner
Essentials Antiphospholipid antibodies (aPL) are heterogeneous and induce different cellular responses. We analyzed signaling events induced by different monoclonal and patient aPL in monocytes. Two major signaling pathways involving either NADPH-oxidase or LRP8 were identified. Our data suggest that these two pathways mediate the majority of aPL effects on monocytes. SUMMARY: Background Antiphospholipid antibodies (aPLs) contribute to the pathogenesis of the antiphospholipid syndrome (APS) by induction of an inflammatory and procoagulant state in different cell types, and several signaling pathways have been described...
October 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29017559/salidroside-protects-against-foam-cell-formation-and-apoptosis-possibly-via-the-mapk-and-akt-signaling-pathways
#14
Jing Ni, Yuanmin Li, Weiming Li, Rong Guo
BACKGROUND: Foam cell formation and apoptosis are closely associated with atherosclerosis pathogenesis. We determined the effect of salidroside on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation and apoptosis in THP1 human acute monocytic leukemia cells and investigated the associated molecular mechanisms. METHODS: THP1-derived macrophages were incubated with salidroside for 5 h and then exposed to ox-LDL for 24 h to induce foam cell formation...
October 10, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28972143/shedding-of-membrane-associated-ldl-receptor-related-protein-1-from-microglia-amplifies-and-sustains-neuroinflammation
#15
Coralie Brifault, Andrew S Gilder, Emilia Laudati, Michael Banki, Steven L Gonias
In the CNS, microglia are activated in response to injury or infection and in neurodegenerative diseases. The endocytic and cell signaling receptor, LDL receptor-related protein-1 (LRP1), is reported to suppress innate immunity in macrophages and oppose microglial activation. The goal of this study was to identify novel mechanisms by which LRP1 may regulate microglial activation. Using primary cultures of microglia isolated from mouse brains, we demonstrated that LRP1 gene silencing increases expression of proinflammatory mediators; however, the observed response was modest...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28966723/extracellular-ldlr-repeats-modulate-wnt-signaling-activity-by-promoting-lrp6-receptor-endocytosis-mediated-by-the-itch-e3-ubiquitin-ligase
#16
Sapna Vijayakumar, Guizhong Liu, Huei-Chi Wen, Yaa Abu, Robert Chong, Horacio Nastri, Gadi G Bornstein, Zhen-Qiang Pan, Stuart A Aaronson
The LOW-density lipoprotein related protein 6 (LRP6) receptor is an important effector of canonical Wnt signaling, a developmental pathway, whose dysregulation has been implicated in various diseases including cancer. The membrane proximal low-density lipoprotein (LDL) receptor repeats in LRP6 exhibit homology to ligand binding repeats in the LDL receptor (LDLR), but lack known function. We generated single amino acid substitutions of LRP6-LDLR repeat residues, which are highly conserved in the human LDLR and mutated in patients with Familial Hypercholesteremia (FH)...
July 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28936395/antioxidative-activity-of-high-density-lipoprotein-hdl-mechanistic-insights-into-potential-clinical-benefit
#17
REVIEW
Fernando Brites, Maximiliano Martin, Isabelle Guillas, Anatol Kontush
Uptake of low-density lipoprotein (LDL) particles by macrophages represents a key step in the development of atherosclerotic plaques, leading to the foam cell formation. Chemical modification of LDL is however necessary to induce this process. Proatherogenic LDL modifications include aggregation, enzymatic digestion and oxidation. LDL oxidation by one-electron (free radicals) and two-electron oxidants dramatically increases LDL affinity to macrophage scavenger receptors, leading to rapid LDL uptake and fatty streak formation...
December 2017: BBA Clinical
https://www.readbyqxmd.com/read/28878222/angiotensin-ii-induces-cholesterol-accumulation-and-injury-in-podocytes
#18
Yingjie Yang, Qian Yang, Jian Yang, Yiqiong Ma, Guohua Ding
Angiotensin II (Ang II) is a risk factor for the initiation and progression of chronic kidney disease (CKD), as elevated Ang II levels can lead to podocyte injury. However, there have been no studies on the role of Ang II in lipid metabolism or on podocyte injury caused by lipid dysfunction. Our study showed that Ang II induced lipid droplet (LD) accumulation and expression of the LD marker adipose differentiation-related protein (ADRP) in podocytes, and the extent of lipid deposition could be alleviated by losartan...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28828729/dr1-activation-reduces-the-proliferation-of-vascular-smooth-muscle-cells-by-jnk-c-jun-dependent-increasing-of-prx3
#19
Junting Chen, Sa Shi, Xiaona Cai, Hongzhu Li, Lina Wang, Hong Li, Changqing Xu
Vascular smooth muscle cells (VSMCs) proliferation is a key process in atherosclerosis. However, little is known about the underlying mechanisms, leading to a lack of effective therapy. This study was to investigate whether dopamine receptor 1 (DR1) is involved in the VSMCs proliferation and related mechanisms. A7r5 cells were treated with oxidized low-density lipoprotein (ox-LDL, 10, 20, 50, 100, 200 µg/mL) in the presence or absence of the SKF38393 (DR1agonist), SCH23390 (DR1antiagonist), SP600125 (JNK inhibitor), PD98059(ERK1/2 inhibitor) or NAC (ROS inhibitor)...
August 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#20
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
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