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Low density lipoprotein receptor related protein 1

Xiaolei Lan, Hua Gao, Fei Wang, Jie Feng, Jiwei Bai, Peng Zhao, Lei Cao, Songbai Gui, Lei Gong, Yazhuo Zhang
Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas...
October 2016: Oncology Letters
Ying Wang, Yongjun Zhang, Meiyu Fang, Wenglong Bao, Dehou Deng
This study investigated the effect of single-nucleotide polymorphisms (SNPs) of low-density lipoprotein receptor-related protein 5 (LRP5) on the risk of developing non-small cell lung cancer (NSCLC). A total of 500 NSCLC patients and 500 healthy controls were recruited for genotyping of 11 SNPs of LRP5. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses. Eleven Tag SNPs were detected...
October 2016: Oncology Letters
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
Yan Ji, Zhen Weng, Philip Fish, Neha Goyal, Mao Luo, Samantha P Myears, Tammy L Strawn, Bysani Chandrasekar, Jianbo Wu, William P Fay
OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor that promotes and inhibits cell migration, plays a complex and important role in adverse vascular remodeling. Little is known about the effects of pharmacological PAI-1 inhibitors, an emerging drug class, on migration of vascular smooth muscle cells (SMCs) and endothelial cells (ECs), crucial mediators of vascular remodeling. We investigated the effects of PAI-039 (tiplaxtinin), a specific PAI-1 inhibitor, on SMC and EC migration in vitro and vascular remodeling in vivo...
September 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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
Daopeng Dai, Weixin Xiong, Qin Fan, Haibo Wang, Qiujing Chen, Weifeng Shen, Ruiyan Zhang, Fenghua Ding, Lin Lu, Rong Tao
Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is closely involved in autoimmune diseases and inflammatory reactions. We aimed to investigate whether serum sTREM-1 is related to coronary artery disease (CAD) and to evaluate the biological effects of sTREM-1 in cell experiments.This cross-sectional study included 263 consecutive patients with angiographically documented CAD, who were admitted for diagnosis and interventional treatment of CAD (CAD group), with 162 participants without CAD serving as controls (control group)...
September 2016: Medicine (Baltimore)
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
Bo Yang, Zhibin Zhou, Xiaohao Li, Jianping Niu
Toll-like receptors (TLRs) are major receptors that mediate the innate immune and inflammatory responses, of which TLR4 has been found most closely related to human atherosclerosis. After ligands are polymerized and activated by TLR, the mitogen-activated protein kinase and nuclear factor-κB (NF-κB) pathways are activated, leading to promotion of NF-κB-regulated transcription of inflammatory factors, thus playing a role in the physiological and pathological processes in atherosclerosis. Oxidized lipoproteins or their components, oxidized lipids, have been confirmed as endogenous TLR receptors...
November 2016: Molecular and Cellular Biochemistry
Sandra Rother, Sergey A Samsonov, Ute Hempel, Sarah Vogel, Stephanie Moeller, Joanna Blaszkiewicz, Sebastian Köhling, Matthias Schnabelrauch, Jörg Rademann, M Teresa Pisabarro, Vera Hintze, Dieter Scharnweber
Sulfated glycosaminoglycans (sGAGs) modulate cellular processes via their interaction with extracellular matrix (ECM) proteins. We revealed a direct binding of tissue inhibitor of metalloproteinase-3 (TIMP-3) to the endocytic receptor low-density lipoprotein receptor-related protein (LRP-1) clusters II and IV using surface plasmon resonance. Sulfated hyaluronan (sHA) and chondroitin sulfate (sCS) derivatives interfered with TIMP-3/LRP-1 complex formation in a sulfation-dependent manner stronger than heparin...
October 10, 2016: Biomacromolecules
Christine M Doherty, Robert Visse, Deendayal Dinakarpandian, Dudley K Strickland, Hideaki Nagase, Linda Troeberg
Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a central inhibitor of matrix-degrading and sheddase families of metalloproteinases. Extracellular levels of the inhibitor are regulated by the balance between its retention on the extracellular matrix and its endocytic clearance by the scavenger receptor low density lipoprotein receptor-related protein 1 (LRP1). Here, we used molecular modeling to predict TIMP-3 residues potentially involved in binding to LRP1 based on the proposed LRP1 binding motif of 2 lysine residues separated by about 21 Å and mutated the candidate lysine residues to alanine individually and in pairs...
October 14, 2016: Journal of Biological Chemistry
Shuichi Nagashima, Kazue Morishima, Hiroaki Okamoto, Shun Ishibashi
Herein, we describe a 69-year-old Japanese man with massive type III hyperlipoproteinemia (total cholesterol, 855 mg/dL; triglyceride, 753 mg/dL) presenting as a paraneoplastic manifestation of hepatitis B virus-associated hepatocellular carcinoma. The messenger RNA expression of sterol regulatory element-binding protein-2 and proprotein convertase subtilisin/kexin 9 in the tumor tissue was increased by 13-fold and 4-fold, respectively, compared with the non-tumor tissue. Serum level of active form of PCSK9 was 382 ng/mL (reference range: 253 ± 79 ng/mL)...
July 2016: Journal of Clinical Lipidology
Yanlan Chen, Wen Huang, Wenlin Jiang, Xianghong Wu, Biao Ye, Xiaoting Zhou
HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Aβ) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining...
2016: Oxidative Medicine and Cellular Longevity
D de Gonzalo-Calvo, D Vilades, L Nasarre, F Carreras, R Leta, X Garcia-Moll, V Llorente-Cortes
No abstract text is available yet for this article.
November 15, 2016: International Journal of Cardiology
Oscar A Marcos-Contreras, Sara Martinez de Lizarrondo, Isabelle Bardou, Cyrille Orset, Mathilde Pruvost, Antoine Anfray, Yvann Frigout, Yannick Hommet, Laurent Lebouvier, Joan Montaner, Denis Vivien, Maxime Gauberti
Hyperfibrinolysis is a systemic condition occurring in various clinical disorders such as trauma, liver cirrhosis or leukemia. Apart from increased bleeding tendency, the pathophysiological consequences of hyperfibrinolysis remain largely unknown. Our present aim was to develop an experimental model of hyperfibrinolysis and to study its effects on the homeostasis of the blood brain barrier (BBB). We induced a sustained hyperfibrinolytic state in mice by hydrodynamic transfection of a plasmid encoding for tissue-type plasminogen activator (tPA)...
August 16, 2016: Blood
B Shackleton, F Crawford, C Bachmeier
BACKGROUND: Transport across the blood-brain barrier (BBB) is an important mediator of beta-amyloid (Aβ) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors responsible for the transport of Aβ in the BBB is the low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at the cell surface, which prevents endocytic transport of ligands. Previously, we reported a strong inverse correlation between LRP1 shedding in the brain and Aβ transit across the BBB...
2016: Fluids and Barriers of the CNS
Yoko Hashimoto, Mari Kobayashi, Etsuko Matsuzaki, Katsumasa Higashi, Fumi Takahashi-Yanaga, Aiko Takano, Masato Hirata, Fusanori Nishimura
In this study, we investigated the involvement of Wnt signaling in sphingosine-1-phosphate (S1P)-enhanced osteogenic differentiation of C3H10T1/2 pluripotent stem cells. We found that S1P enhanced the expression of Wnt5a and low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6) during osteogenic differentiation. Wnt5a-neutralizing antibody inhibited S1P-enhanced expression of LRP5/6 and alkaline phosphatase, which are essential for osteogenic differentiation. Conversely, S1P did not affect endogenous canonical Wnt signaling...
October 2016: Cell Biology International
Patrícia Figueiredo, Vimalkumar Balasubramanian, Mohammad-Ali Shahbazi, Alexandra Correia, Dalin Wu, Cornelia G Palivan, Jouni T Hirvonen, Hélder A Santos
A targeted drug delivery nanosystem for glioblastoma multiforme (GBM) based on polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS-PMOXA) diblock copolymers was developed to evaluate their potential to actively target brain cancer cells and deliver anticancer drugs. Angiopep2 was conjugated to the surface of preformed Ps to target the low density lipoprotein receptor-related protein 1 that are overexpressed in blood brain barrier (BBB) and glioma cells. The conjugation efficiency yield for angiopep2 was estimated to be 24%...
September 25, 2016: International Journal of Pharmaceutics
Simone D Scilabra, Kazuhiro Yamamoto, Martina Pigoni, Kazuma Sakamoto, Stephan A Müller, Alkmini Papadopoulou, Stefan F Lichtenthaler, Linda Troeberg, Hideaki Nagase, Kenji Kadomatsu
Tissue inhibitor of metalloproteinases 3 (TIMP-3) is a key regulator of extracellular matrix turnover for its ability to inhibit matrix metalloproteinases (MMPs), adamalysin-like metalloproteinases (ADAMs) and ADAMs with thrombospondin motifs (ADAMTSs). TIMP-3 is a secreted protein whose extracellular levels are regulated by endocytosis via the low-density-lipoprotein receptor-related protein-1 (LRP-1). In this study we developed a molecule able to "trap" TIMP-3 extracellularly, thereby increasing its tissue bioavailability...
July 29, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Peter G W Gettins, Steven T Olson
Serpins are a widely distributed family of high molecular mass protein proteinase inhibitors that can inhibit both serine and cysteine proteinases by a remarkable mechanism-based kinetic trapping of an acyl or thioacyl enzyme intermediate that involves massive conformational transformation. The trapping is based on distortion of the proteinase in the complex, with energy derived from the unique metastability of the active serpin. Serpins are the favoured inhibitors for regulation of proteinases in complex proteolytic cascades, such as are involved in blood coagulation, fibrinolysis and complement activation, by virtue of the ability to modulate their specificity and reactivity...
August 1, 2016: Biochemical Journal
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