ldl receptors

Summary

Summary: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.

Top Publications

  1. ncbi LDL-receptor-related protein 6 is a receptor for Dickkopf proteins
    B Mao
    Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Nature 411:321-5. 2001
  2. pmc Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery
    S Ishibashi
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235
    J Clin Invest 92:883-93. 1993
  3. ncbi Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction
    Gary Davidson
    Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Nature 438:867-72. 2005
  4. ncbi Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation
    Da Wei Zhang
    Department of Molecular Genetics, The Donald W Reynolds Cardiovascular Clinical Research Center, Howard Hughes Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 282:18602-12. 2007
  5. ncbi Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins
    Weijia Kong
    Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, 100050, China
    Nat Med 10:1344-51. 2004
  6. pmc Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice
    Thomas A Lagace
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 116:2995-3005. 2006
  7. ncbi A receptor-mediated pathway for cholesterol homeostasis
    M S Brown
    Science 232:34-47. 1986
  8. ncbi Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia
    David Cunningham
    Pfizer Inc, Eastern Point Road, Groton, Connecticut 06430, USA
    Nat Struct Mol Biol 14:413-9. 2007
  9. ncbi NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 279:48865-75. 2004
  10. ncbi Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6
    M V Semenov
    Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Curr Biol 11:951-61. 2001

Detail Information

Publications288 found, 100 shown here

  1. ncbi LDL-receptor-related protein 6 is a receptor for Dickkopf proteins
    B Mao
    Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Nature 411:321-5. 2001
    ..Thus, DKKs inhibit Wnt co-receptor function, exemplifying the modulation of LRP signalling by antagonists...
  2. pmc Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery
    S Ishibashi
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235
    J Clin Invest 92:883-93. 1993
    ..Homozygous male and female mice lacking LDL receptors (LDLR-/- mice) were viable and fertile...
  3. ncbi Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction
    Gary Davidson
    Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Nature 438:867-72. 2005
    ..Our results reveal an evolutionarily conserved mechanism that couples Wnt receptor activation to the cytoplasmic signal transduction apparatus...
  4. ncbi Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation
    Da Wei Zhang
    Department of Molecular Genetics, The Donald W Reynolds Cardiovascular Clinical Research Center, Howard Hughes Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 282:18602-12. 2007
    ..As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded...
  5. ncbi Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins
    Weijia Kong
    Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, 100050, China
    Nat Med 10:1344-51. 2004
    ..These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs...
  6. pmc Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice
    Thomas A Lagace
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 116:2995-3005. 2006
    ..type 9 (PCSK9) is a member of the proteinase K subfamily of subtilases that reduces the number of LDL receptors (LDLRs) in liver through an undefined posttranscriptional mechanism...
  7. ncbi A receptor-mediated pathway for cholesterol homeostasis
    M S Brown
    Science 232:34-47. 1986
  8. ncbi Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia
    David Cunningham
    Pfizer Inc, Eastern Point Road, Groton, Connecticut 06430, USA
    Nat Struct Mol Biol 14:413-9. 2007
    ..PCSK9 may diminish LDL receptors by a mechanism that requires direct binding but not necessarily receptor proteolysis.
  9. ncbi NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 279:48865-75. 2004
    ..In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion...
  10. ncbi Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6
    M V Semenov
    Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Curr Biol 11:951-61. 2001
    ..The significance of the Fz-LRP6 complex in signal transduction remains to be established...
  11. ncbi Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions
    Xin Zeng
    The F M Kirby Neurobiology Center, Children s Hospital Boston, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Development 135:367-75. 2008
    ..We discuss the dual roles of the axin-Gsk3 complex and signal amplification by Lrp6-axin interaction during Wnt/beta-catenin signaling...
  12. ncbi Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation
    T Hiesberger
    Department of Molecular Genetics, UT Southwestern Dallas, Texas 75235, USA
    Neuron 24:481-9. 1999
    ..Taken together, these findings suggest that Reelin acts via VLDLR and ApoER2 to regulate Disabled-1 tyrosine phosphorylation and microtubule function in neurons...
  13. pmc Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification
    Kym M Boycott
    Department of Medical Genetics, Alberta Children s Hospital and University of Calgary, Alberta, Canada
    Am J Hum Genet 77:477-83. 2005
    ..To our knowledge, this syndrome represents the first human lipoprotein receptor malformation syndrome and the second human disease associated with a reelin pathway defect...
  14. ncbi Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2
    M Trommsdorff
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235 9046, USA
    Cell 97:689-701. 1999
    ..These findings suggest that VLDLR and ApoER2 participate in transmitting the extracellular Reelin signal to intracellular signaling processes initiated by mDab1...
  15. ncbi The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2
    Steve Poirier
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 283:2363-72. 2008
    ..Thus, this study demonstrates a more general effect of PCSK9 on the degradation of the LDLR family that emphasizes its major role in cholesterol and lipid homeostasis as well as brain development...
  16. pmc Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor
    Masaki Kato
    Department of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    J Cell Biol 157:303-14. 2002
    ..Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation...
  17. pmc Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density
    Liesbeth Van Wesenbeeck
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 72:763-71. 2003
    ..Functional analysis of the effects of the various mutations will be of interest, to evaluate whether all the mutations give rise to the same pathogenic mechanism...
  18. ncbi Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway
    J Mao
    Department of Genetics and Developmental Biology, University of Connecticut, Farmington, CT 06030, USA
    Mol Cell 7:801-9. 2001
    ..In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway...
  19. ncbi The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR
    Nasha Nassoury
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7
    Traffic 8:718-32. 2007
    ..Mutations that affect this transport can lead to hyper- or hypocholesterolemia...
  20. ncbi Reelin is a ligand for lipoprotein receptors
    G D'ARCANGELO
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Neuron 24:471-9. 1999
    ..In dissociated neurons, apoE reduces the level of Reelin-induced tyrosine phosphorylation of Dab1. These data suggest that Reelin directs neuronal migration by binding to VLDLR and ApoER2...
  21. pmc Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9
    Shirya Rashid
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 102:5374-9. 2005
    ..These data demonstrate that PCSK9 regulates the amount of LDLR protein in liver and suggest that inhibitors of PCSK9 may act synergistically with statins to enhance LDLRs and reduce plasma cholesterol...
  22. ncbi Apolipoprotein E: cholesterol transport protein with expanding role in cell biology
    R W Mahley
    Gladstone Foundation Laboratories for Cardiovascular Disease, University of California, San Francisco 94140 0608
    Science 240:622-30. 1988
    ..Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation...
  23. ncbi Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation
    Donald A Glass
    Department of Molecular and Human Genetics, Bone Disease Program of Texas, Houston, 77030, USA
    Dev Cell 8:751-64. 2005
    ....
  24. ncbi Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein
    M Trommsdorff
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235 9046, USA
    J Biol Chem 273:33556-60. 1998
    ....
  25. pmc Modulation of amyloid beta-protein clearance and Alzheimer's disease susceptibility by the LDL receptor-related protein pathway
    D E Kang
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA
    J Clin Invest 106:1159-66. 2000
    ..Although LRP has been proposed to be a clearance pathway for Abeta, this work provides the first in vivo evidence that the LRP pathway may modulate Abeta deposition and AD susceptibility by regulating the removal of soluble Abeta...
  26. ncbi LDL-receptor-related proteins in Wnt signal transduction
    K Tamai
    Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 407:530-5. 2000
    ..The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex...
  27. pmc Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1
    Qiang Liu
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 56:66-78. 2007
    ....
  28. pmc Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype
    Kara N Maxwell
    Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 101:7100-5. 2004
    ....
  29. pmc Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance
    Jungsu Kim
    Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 64:632-44. 2009
    ..Plaque-associated neuroinflammatory responses were attenuated in LDLR transgenic mice. These findings suggest that increasing LDLR levels may represent a novel AD treatment strategy...
  30. pmc High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice
    Lakshmi Thirumangalakudi
    Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Neurochem 106:475-85. 2008
    ..The findings link hypercholesterolemia with cognitive dysfunction potentially mediated by increased neuroinflammation and APP processing in a non-transgenic mouse model...
  31. ncbi Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling
    Xiaofeng Li
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, 06030, USA
    J Biol Chem 280:19883-7. 2005
    ....
  32. pmc Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice
    U Schonbeck
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, LMRC 309, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 97:7458-63. 2000
    ..This study lends further support to the importance of this specific inflammatory signaling pathway in atherosclerosis and its complications...
  33. ncbi Lipoprotein receptors in the nervous system
    Joachim Herz
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390, USA
    Annu Rev Biochem 71:405-34. 2002
    ....
  34. ncbi The LDL receptor-related protein (LRP) family: an old family of proteins with new physiological functions
    Petra May
    Universitat Freiburg, Medizinische Klinik II Zentrum für Neurowissenschaften, Freiburg, Germany
    Ann Med 39:219-28. 2007
    ....
  35. pmc The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd
    Yazhou Zhang
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06410, USA
    Mol Cell Biol 24:4677-84. 2004
    ....
  36. pmc Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route
    Steve Poirier
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 284:28856-64. 2009
    ..Therefore, targeting either pathway, or both, would be an effective method to reduce PCSK9 activity in the treatment of hypercholesterolemia and coronary heart disease...
  37. ncbi The mammalian low-density lipoprotein receptor family
    M M Hussain
    Department of Biochemistry, MCP Hahnemann University, Philadelphia, Pennsylvania 19129, USA
    Annu Rev Nutr 19:141-72. 1999
    ..It is anticipated that increased knowledge about the LDL-R family members will open new avenues for the treatment of many disorders...
  38. ncbi Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway
    Sanyong Niu
    The Cain Foundation Laboratories, Houston, TX 77030, USA
    Neuron 41:71-84. 2004
    ..Thus, the same signaling pathway controls both neuronal migration and dendrite maturation...
  39. ncbi The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH
    Meghan E Maurer
    Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA
    J Cell Sci 119:4235-46. 2006
    ....
  40. ncbi Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation
    Timothy S Fisher
    Department of Cardiovascular Diseases, Merck Research Laboratories, Rahway, NJ 07065, USA
    J Biol Chem 282:20502-12. 2007
    ..Together, the results of our biochemical and cell-based experiments suggest a model in which secreted PCSK9 binds to LDLR and directs the trafficking of LDLR to the lysosomes for degradation...
  41. ncbi Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells
    Markey C McNutt
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 282:20799-803. 2007
    ..We conclude that the ability of PCSK9 to degrade LDLRs is independent of catalytic activity and suggest that PCSK9 functions as a chaperone to prevent LDLR recycling and/or to target LDLRs for lysosomal degradation...
  42. ncbi Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling
    Bingyu Mao
    Molecular Embryology Division, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Nature 417:664-7. 2002
    ..The results indicate that Kremen1 and Kremen2 are components of a membrane complex modulating canonical Wnt signalling through LRP6 in vertebrates...
  43. ncbi Human prostate cancer cells lack feedback regulation of low-density lipoprotein receptor and its regulator, SREBP2
    Y Chen
    Laboratory of Cell Growth, University of California San Francisco and Veterans Affairs Medical Center, USA
    Int J Cancer 91:41-5. 2001
    ..The data also suggest that the sterol regulatory element and SREBP2 play a role in the loss of sterol feedback regulation in cancer cells...
  44. ncbi Identification of scavenger receptor SR-BI as a high density lipoprotein receptor
    S Acton
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Science 271:518-20. 1996
    ..SR-BI binds HDL with high affinity, is expressed primarily in liver and nonplacental steroidogenic tissues, and mediates selective cholesterol uptake by a mechanism distinct from the classic LDL receptor pathway...
  45. pmc Molecular basis for LDL receptor recognition by PCSK9
    Hyock Joo Kwon
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 9050, USA
    Proc Natl Acad Sci U S A 105:1820-5. 2008
    ....
  46. ncbi Divergent roles of ApoER2 and Vldlr in the migration of cortical neurons
    Iris Hack
    Institut fur Anatomie und Zellbiologie, Albert Ludwigs Universitat Freiburg, D 79104 Freiburg, Germany
    Development 134:3883-91. 2007
    ..We present evidence for divergent roles of the two reelin receptors Vldlr and ApoER2, with Vldlr mediating a stop signal for migrating neurons and ApoER2 being essential for the migration of late generated neocortical neurons...
  47. ncbi The apoE isoform binding properties of the VLDL receptor reveal marked differences from LRP and the LDL receptor
    Jose Ruiz
    Department of Surgery, University of Maryland School of Medicine, Rockville, MD 21201, USA
    J Lipid Res 46:1721-31. 2005
    ..It is likely that this receptor-dependent specificity for various apoE isoforms and for lipid-free versus lipid-bound forms of apoE is physiologically significant and is connected to distinct functions for these receptors...
  48. pmc Sex-dependent association of a common low-density lipoprotein receptor polymorphism with RNA splicing efficiency in the brain and Alzheimer's disease
    Fanggeng Zou
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Hum Mol Genet 17:929-35. 2008
    ..49, 95% confidence interval (CI) of 1.13-1.97, uncorrected P = 0.005], but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion...
  49. ncbi Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair
    H Jeon
    Brigham Women s Hospital and Harvard Medical School Department of Pathology, 75 Francis Street, Boston, Massachusetts 02115, USA
    Nat Struct Biol 8:499-504. 2001
    ..A second subset of FH mutations are located at the interface between the propeller and the C-terminal EGF module, suggesting a structural requirement for maintaining the integrity of the interdomain interface...
  50. pmc Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk
    S E Humphries
    J Med Genet 43:943-9. 2006
    ..Patients and..
  51. ncbi Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis
    Yue Wei Qian
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    J Lipid Res 48:1488-98. 2007
    ....
  52. ncbi Berberine decreases PCSK9 expression in HepG2 cells
    Jamie Cameron
    Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway
    Atherosclerosis 201:266-73. 2008
    ..Mutations in the PCSK9 gene have been shown to cause either hypo- or hypercholesterolemia. Here we investigated the effect of berberine, a natural plant extract, on PCSK9 expression in HepG2 cells...
  53. ncbi Phosphatidylinositol 3-kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for normal cortical lamination
    Hans H Bock
    Department of Molecular Genetics and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390 9046, USA
    J Biol Chem 278:38772-9. 2003
    ..Using a neuronal migration assay, we also show that PI3K signaling is required for the formation of a normal cortical plate, a step that is dependent upon Reelin signaling...
  54. ncbi Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI
    M Krieger
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Annu Rev Biochem 68:523-58. 1999
    ..SR-BI may play a similar role in humans; thus, modulation of its activity may provide the basis of future approaches to the treatment and prevention of atherosclerotic disease...
  55. ncbi The low-density lipoprotein receptor gene family: a cellular Swiss army knife?
    Anders Nykjaer
    Dept of Medical Biochemistry, University of Aarhus, DK 8000, Aarhus C, Denmark
    Trends Cell Biol 12:273-80. 2002
    ..Here, we review the molecular interactions of this protein family with other cell-surface proteins that provide specificity and versatility - a versatility that may be reminiscent of a cellular Swiss army knife...
  56. pmc Endocytic trafficking of megalin/RAP complexes: dissociation of the complexes in late endosomes
    R P Czekay
    Division of Cellular and Molecular Medicine, University of California San Diego, La Jolla 92093, USA
    Mol Biol Cell 8:517-32. 1997
    ..We conclude that in contrast to receptor/ligand complexes, megalin/RAP complexes traffic through late endosomes, which is a novelty for members of the low-density lipoprotein receptor gene family...
  57. ncbi Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response
    Rossi P Naoumova
    MRC Clinical Sciences Centre, Hammersmith Hospital, London W12 0NN, UK
    Arterioscler Thromb Vasc Biol 25:2654-60. 2005
    ....
  58. ncbi LDL-receptor mutations in Europe
    George V Z Dedoussis
    Department of Science Dietetics Nutrition, Harokopio University of Athens, Athens, Greece
    Hum Mutat 24:443-59. 2004
    ..Herein, we focus on the published European LDLR mutation data that reflect its heterogeneity and phenotypic penetrance...
  59. ncbi Distribution of lipid deposits around aortic branches of mice lacking LDL receptors and apolipoprotein E
    C J McGillicuddy
    School of Animal and Microbial Sciences, University of Reading, Reading, UK
    Arterioscler Thromb Vasc Biol 21:1220-5. 2001
    ..We conclude that knockout mice may not be a suitable model in which to investigate localizing factors...
  60. ncbi Long-term stable expression of human apolipoprotein A-I mediated by helper-dependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia
    L Maria Belalcazar
    Department of Medicine, University of Texas Medical Branch, Galveston, Tex, USA
    Circulation 107:2726-32. 2003
    ..We used helper-dependent adenovirus (HD-Ad) gene transfer to examine the effect of long-term hepatic apoA-I expression on atherosclerotic lesion progression and remodeling in a mouse model of familial hypercholesterolemia...
  61. ncbi Structure and physiologic function of the low-density lipoprotein receptor
    Hyesung Jeon
    Life Sciences Division, Korea Institute of Science and Technology, Seoul 136 791, Korea
    Annu Rev Biochem 74:535-62. 2005
    ....
  62. pmc Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor
    V Agnello
    Lahey Clinic Medical Center, Department of Laboratory Medicine, Burlington, MA 01805, USA
    Proc Natl Acad Sci U S A 96:12766-71. 1999
    ..These findings provide evidence that the family of LDL receptors may serve as viral receptors.
  63. ncbi The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA
    T Yamamoto
    Cell 39:27-38. 1984
    ..Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors...
  64. ncbi Pharmacotherapy for dyslipidaemia--current therapies and future agents
    Harold Bays
    L MARC Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA
    Expert Opin Pharmacother 4:1901-38. 2003
    ..Finally, current and future lipid-altering drugs may include anti-obesity agents which could favourably affect lipid levels...
  65. ncbi Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity
    Jen Chih Hsieh
    Department of Biochemistry and Cell Biology, Center for Developmental Genetics, State University of New York, Stony Brook, Stony Brook, NY 11794, USA
    Cell 112:355-67. 2003
    ....
  66. ncbi Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low density lipoprotein receptor family member
    H Yamazaki
    Second Department of Internal Medicine, Chiba University School of Medicine, Chiba 260, Japan
    J Biol Chem 271:24761-8. 1996
    ..The identification of this highly conserved and superbly complex protein offers the opportunity to gain new insights into the emergence of multifunctional mosaic proteins akin to the ever expanding LDL receptor gene family...
  67. ncbi The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppØ sorting signals at distinct sites
    Werner Boll
    Department of Cell Biology and The Center for Blood Research, Harvard Medical School, 200 Longwood Ave, Boston, MA, 02115, USA
    Traffic 3:590-600. 2002
    ..These results suggest the possibility that low-density lipoprotein receptor uptake may be modulated specifically and independently of other proteins in the clathrin pathway...
  68. ncbi Peroxisome proliferator-activated receptor-alpha selective ligand reduces adiposity, improves insulin sensitivity and inhibits atherosclerosis in LDL receptor-deficient mice
    Rai Ajit K Srivastava
    CloneGen Biotechnology, Ann Arbor, MI, USA
    Mol Cell Biochem 285:35-50. 2006
    ..These results suggest that potent PPAR-alpha activators may be useful in the treatment of syndrome X...
  69. pmc A novel mechanism for Wnt activation of canonical signaling through the LRP6 receptor
    Guizhong Liu
    Derald H Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA
    Mol Cell Biol 23:5825-35. 2003
    ..Thus, Wnt canonical signaling through LRP6 establishes a novel mechanism for receptor activation which is opposite to the general paradigm of ligand-induced receptor oligomerization...
  70. ncbi Effects of L-triiodothyronine and the thyromimetic L-94901 on serum lipoprotein levels and hepatic low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and apo A-I gene expression
    G C Ness
    Department of Biochemistry and Molecular Biology, College of Medicine and the Institute for Biomolecular Science, University of South Florida, Tampa 33612, USA
    Biochem Pharmacol 56:121-9. 1998
    ..In contrast with most other hypocholesterolemic agents, T3 and L-94901 significantly increase HDL cholesterol levels in addition to decreasing LDL cholesterol levels due to induction of hepatic apo A-I and LDL receptor gene expression...
  71. ncbi Binding and uptake of chylomicron remnants by primary and THP-1 human monocyte-derived macrophages: determination of binding proteins
    C L Elsegood
    Department of Physiology, The University of Western Australia, Perth, Western Australia 6907, Australia
    Clin Sci (Lond) 101:111-9. 2001
    ..We propose that the 43 kDa macrophage chylomicron remnant binding protein may be a candidate for the sterol loading of macrophages...
  72. ncbi Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands
    M A Umans-Eckenhausen
    Foundation for the Identification of Persons with Inherited Hypercholesterolaemia, Amsterdam, The Netherlands
    Lancet 357:165-8. 2001
    ..Our findings could have wider relevance for the screening of other prevalent genetic disorders in the population at large...
  73. pmc Plasma PCSK9 preferentially reduces liver LDL receptors in mice
    Aldo Grefhorst
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9046, USA
    J Lipid Res 49:1303-11. 2008
    ....
  74. ncbi A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease
    Andreas Papassotiropoulos
    Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
    J Clin Psychiatry 66:940-7. 2005
    ..Polygenic diseases are related to the complex interplay of genetic variations. We evaluated whether clusters of cholesterol- and lipid-related genetic variations are associated with Alzheimer's disease...
  75. pmc Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment
    Kara N Maxwell
    Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 102:2069-74. 2005
    ..These results indicate that overexpression of PCSK9 induces the degradation of the LDLR by a nonproteasomal mechanism in a post-endoplasmic reticulum compartment...
  76. pmc A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol
    Haiyan Zhu
    Department of Physiology and Sanders Brown Center on Aging, 800 S Limestone Street, University of Kentucky, Lexington, KY 40536 0230, USA
    Hum Mol Genet 16:1765-72. 2007
    ..In summary, these studies identify an LDLR SNP present in approximately 60% of Caucasians that is associated with significant 10% increases in total and LDL-cholesterol in pre-menopausal women...
  77. pmc A neuronal VLDLR variant lacking the third complement-type repeat exhibits high capacity binding of apoE containing lipoproteins
    Keiko Sakai
    Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
    Brain Res 1276:11-21. 2009
    ..These results suggest that a VLDLR variant lacking the third complement-type repeat is generated by neuron-specific alternative splicing. Such differential splicing may result in different lipid uptake in neurons and astrocytes...
  78. ncbi The low-density lipoprotein receptor gene family: multiple roles in lipid metabolism
    T E Willnow
    Max Delbruck Center, Berlin, Germany
    J Mol Med (Berl) 77:306-15. 1999
    ..and adipositas...
  79. ncbi An LDL-receptor-related protein mediates Wnt signalling in mice
    K I Pinson
    Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA
    Nature 407:535-8. 2000
    ..Furthermore, we show a genetic enhancement of a Wnt mutant phenotype in mice lacking one functional copy of LRP6. Together, our results support a broad role for LRP6 in the transduction of several Wnt signals in mammals...
  80. pmc Adipocyte LDL receptor-related protein-1 expression modulates postprandial lipid transport and glucose homeostasis in mice
    Susanna M Hofmann
    Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45237, USA
    J Clin Invest 117:3271-82. 2007
    ..These findings identify LRP1 as a critical regulator of adipocyte energy homeostasis, where functional disruption leads to reduced lipid transport, increased insulin sensitivity, and muscular energy expenditure...
  81. ncbi The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits
    Rita Garuti
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 8591, USA
    J Biol Chem 280:40996-1004. 2005
    ..These results demonstrate that ARH must bind the LDLR tail and either clathrin or AP-2 to promote receptor clustering and internalization of LDL...
  82. ncbi Proprotein convertase subtilisin kexin 9: the third locus implicated in autosomal dominant hypercholesterolemia
    Kara N Maxwell
    Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021, USA
    Curr Opin Lipidol 16:167-72. 2005
    ..Identification and study of the causative genes in these families should provide additional insights into LDL metabolism...
  83. ncbi The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors
    C G Davis
    Cell 45:15-24. 1986
    ..These results support the hypothesis that cytoplasmic domains direct receptors to coated pits, thereby determining the high rate of receptor internalization in animal cells...
  84. ncbi Binding of purified Reelin to ApoER2 and VLDLR mediates tyrosine phosphorylation of Disabled-1
    David Benhayon
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Brain Res Mol Brain Res 112:33-45. 2003
    ..These findings demonstrate that ApoER2 and VLDLR are essential for Reelin signaling and that no other receptor molecules can compensate for their role in mediating tyrosine phosphorylation of Dab1...
  85. pmc Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1
    M Accad
    Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141, USA
    J Clin Invest 105:711-9. 2000
    ....
  86. ncbi A mechanism for Wnt coreceptor activation
    Keiko Tamai
    Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 13:149-56. 2004
    ..Our study identifies a critical signaling module and a key phosphorylation-dependent activation step of the Wnt receptor complex and reveals a unifying logic for transmembrane signaling by Wnts, growth factors, and cytokines...
  87. pmc Tumor necrosis factor receptor-associated factor 1 (TRAF1) deficiency attenuates atherosclerosis in mice by impairing monocyte recruitment to the vessel wall
    Anna Missiou
    Department of Cardiology, University of Freiburg, Germany
    Circulation 121:2033-44. 2010
    ..Tumor necrosis factor receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins for this group of cytokines...
  88. pmc Role of the low density lipoprotein receptor in the flux of cholesterol through the plasma and across the tissues of the mouse
    Y Osono
    Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235
    J Clin Invest 95:1124-32. 1995
    ..Changes in LDLR activity, therefore, profoundly alter the plasma LDL-C concentration but have virtually no affect on cholesterol balance across any extrahepatic organ, including the brain...
  89. ncbi Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice
    Dongfeng Cao
    Atherosclerosis Research Unit, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Alabama at Birmingham, 1530 3rd Avenue South, BDB 658, Birmingham, AL 35294, USA
    Neurobiol Aging 27:1632-43. 2006
    ..Our results suggest that the LDLR plays a role in the development of Alzheimer-type learning impairment and amyloidosis and can be a novel therapeutic target for AD...
  90. ncbi Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate
    A H Lichtman
    Vascular Research Division, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Arterioscler Thromb Vasc Biol 19:1938-44. 1999
    ..This study shows that sodium cholate is not necessary for the formation of atherosclerosis in LDLR(-/-) mice and that precisely defined semipurified diets are a valuable tool for the examination of diet-gene interactions...
  91. ncbi Lipoprotein receptors: new roles for ancient proteins
    T E Willnow
    Max Delbruck Center for Molecular Medicine, R Rossle Strasse 10, 13125 Berlin, Germany
    Nat Cell Biol 1:E157-62. 1999
    ..Other members of this receptor family interact with cytosolic signalling proteins, giving this evolutionarily ancient family of receptors an entirely unexpected new role as transducers of extracellular signals...
  92. ncbi Dual regulation of the LDL receptor--some clarity and new questions
    Alan D Attie
    Department of Biochemistry, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    Cell Metab 1:290-2. 2005
    ..While the mRNA expression of the LDLR and the newly studied proprotein convertase PCSK9 are coordinately upregulated in absence of sterols, the latter proteinase apparently enhances the degradation of the LDLR protein...
  93. ncbi Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6
    Bryan T MacDonald
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 0618, USA
    Development 131:2543-52. 2004
    ..These compensatory interactions between Dkk1 and Lrp6 demonstrate the importance of correctly balancing positive and negative regulation of Wnt signaling during mammalian development...
  94. ncbi The LDL receptor gene: a mosaic of exons shared with different proteins
    T C Sudhof
    Science 228:815-22. 1985
    ..The LDL receptor appears to be a mosaic protein built up of exons shared with different proteins, and it therefore belongs to several supergene families...
  95. ncbi Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow
    A Bafico
    Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, Box 1130, One Gustave L. Levy Place, New York, New York 10029, USA
    Nat Cell Biol 3:683-6. 2001
    ....
  96. ncbi The molecular basis of familial hypercholesterolemia in The Netherlands
    S W Fouchier
    Department of Vascular Medicine G1 112b, Academic Medical Center at the University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands
    Hum Genet 109:602-15. 2001
    ....
  97. ncbi Mice deficient in apolipoprotein E but not LDL receptors are resistant to accelerated atherosclerosis associated with obesity
    Sandra A Schreyer
    Department of Cell Biology and Biochemistry, AstraZeneca, Molndal, Sweden
    Atherosclerosis 171:49-55. 2003
    ....
  98. ncbi LDL-receptor mRNA expression in men is downregulated within an hour of an acute fat load and is influenced by genetic polymorphism
    Anothai Pocathikorn
    Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia 6000
    J Nutr 137:2062-7. 2007
    ..It documents immediate effects of a fatty meal on these mRNA as well as an LRP genotype effect on LDLR mRNA and LDL-C...
  99. ncbi LRP5/6 in Wnt signaling and tumorigenesis
    Yonghe Li
    Southern Research Institute, Biochemistry and Molecular Biology Department, Drug Discovery Division, Birmingham, AL 35255, USA
    Future Oncol 1:673-81. 2005
    ..Furthermore, it has been demonstrated that LRP5 and 6 are potential oncogenic proteins. Thus, blockade of LRP56 function may lead to new strategies in cancer treatment...
  100. ncbi The 39-kDa receptor-associated protein modulates lipoprotein catabolism by binding to LDL receptors
    J D Medh
    Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
    J Biol Chem 270:536-40. 1995
    ..Here, we show that RAP binds to LDL receptors as well...
  101. pmc A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation
    Xin Zeng
    Neurobiology Program, Children s Hospital Boston, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 438:873-7. 2005
    ....

Research Grants74

  1. Antiphospholipid antibodies and lupus: new molecular targets for treatment
    Emilio B Gonzalez; Fiscal Year: 2013
    ..These studies may help to devise new more specific and less harmful modalities than the anticoagulation or general immunosuppression currently used to treat and prevent thrombosis in patients with aPL Abs. ..
  2. Agrin/alpha 3 Na,K-ATPase signaling at the neuromuscular junction
    Martin A Smith; Fiscal Year: 2012
    ..This novel signal pathway represents a new therapeutic target for the treatment of neuromuscular disease. ..
  3. Response to and signals of caloric restriction and intermittent feeding regimens
    MARC KOPEL HELLERSTEIN; Fiscal Year: 2010
    ....
  4. Genetic and physiological causes of inherited Vascular and Metabolic Diseases
    Arya Mani; Fiscal Year: 2013
    ..The current study goals are investigating the effect of the mutation on metabolism of glucose and insulin secretion and function in patients with this mutation. ..
  5. Prolonged Inhibition of Pathologic Neovascularization by Catalytic Antioxidants
    JAMES FRANCIS MCGINNIS; Fiscal Year: 2013
    ....
  6. The genetics and pathophysiology of impaired Wnt signaling in metabolic syndrome
    Arya Mani; Fiscal Year: 2012
    ..Moreover, we plan to screen number of families with inherited CAD, metabolic syndrome, and osteoporosis for mutations within this gene to identify novel mutations and to investigate their disease causing mechanisms. ..
  7. Role of MicroRNA mi R-33 in Controlling Cholesterol/Lipid Homeostasis
    Anders M Naar; Fiscal Year: 2010
    ..These studies should provide novel therapeutic strategies aimed at increasing HDL synthesis and cholesterol clearance in patients with cardiovascular disease. ..
  8. Development of a Porcine Model of Atherosclerosis
    Christopher Rogers; Fiscal Year: 2010
    ..This animal model will provide academic and industrial research communities with an opportunity to better understand cardiovascular disease and its pathogenesis, and to develop and test new therapeutics and preventative strategies. ..
  9. The Postischemia Inflammatory Syndrome in the Aged Kidney
    KATHERINE JULIA KELLY; Fiscal Year: 2013
    ..Nearly one-half of patient beginning dialysis for CKD were e65 yo. We propose to study inflammatory and vascular injury and cell death and the effects of potential therapies in a model of CKD. ..
  10. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
    ....
  11. Development of a Porcine Model of Atherosclerosis
    Christopher Rogers; Fiscal Year: 2012
    ..Thus, this work will accelerate the discovery of novel therapies for this costly and deadly disease. ..
  12. Regulation of Signaling Receptor Activity by LRP-1
    Steven L Gonias; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Low density lipoprotein receptor-related protein has emerged as an important regulator of inflammation and atherosclerosis. This proposal seeks to elucidate the responsible mechanisms. ..
  13. Lipoprotein Structure and Function by Individual Particle Electron Tomography
    Gang Ren; Fiscal Year: 2013
    ..one molecule of apolipoprotein B-100 (apoB-100), a ligand for hepatic clearance of plasma cholesterol via LDL receptors. HDL sequesters cholesterol from peripheral tissues, including the arterial wall, and transports it to the ..
  14. Interactions of Diesel Exhaust and Respiratory Viruses in Asthmatic Children
    Toby C Lewis; Fiscal Year: 2013
    ..2 million people in the United States, thus pointing the way towards targeted therapies and public health approaches. ..
  15. Macrophage AMPK, Inflammation, and Atherosclerosis
    Bingzhong Xue; Fiscal Year: 2013
    ..Completing these studies will greatly improve our knowledge on the role of macrophage AMPK in the protection against inflammation-associated metabolic disorders, including atherosclerosis and insulin resistance. ..
  16. Age-Related Decrease in A-Beta Peptide Clearance Pathways: CSF and BBB
    Conrad Earl Johanson; Fiscal Year: 2010
    ..Translation: Ap is an expedient marker to analyze aging effects on ISF-CSF relationships, and the compromised solute clearance by malfunctioning barrier systems. This sheds light on neurodegeneration. ..
  17. Plasminogen activators and NMDA after brain injury
    William M Armstead; Fiscal Year: 2012
    ..Immunohistochemistry, detection of plasminogen activator and MAPK expression, and CBF determination by radiolabled microspheres will be performed. ..
  18. Prevention of high fat diet-induced vascular injury
    Ming Hui Zou; Fiscal Year: 2013
    ..It is anticipated that the completion of this project will yield important insights into how omega-3 polyunsaturated fatty acids protect against cardiovascular diseases. ..
  19. TRANSGENIC ANALYSIS OF PLATELET RECEPTOR EXPRESSION
    Jerry Ware; Fiscal Year: 2012
    ..An understanding of how platelets function in the process will lead to better therapeutic strategies and improved health in the U.S. ..
  20. BRAIN LIPID METABOLISM, DENDRITES AND SYNAPSES IN AGING AND ALZHEIMER'S DISEASE
    Guojun Bu; Fiscal Year: 2013
    ..Our studies may also define apoE and apoE receptors as critical targets for AD therapy. ..
  21. Plasmalogen-derived bioactive lipids in atherosclerosis
    David A Ford; Fiscal Year: 2013
    ..In this proposal we will test the hypothesis that novel chlorinated lipid species are important mediators of atherosclerosis. ..
  22. Mouse Models to Characterize the Role of Lrp6 in Metabolic Syndrome
    Bart O Williams; Fiscal Year: 2010
    ..Given that cardiovascular disease is the leading killer in the United States, this work will be very significant in gaining a better understanding of the underlying causes of this disease. ..
  23. Abdominal Adipose Tissue Inflammation
    Peter S Tobias; Fiscal Year: 2013
    ..Collectively, these studies will provide key insight into an extreme atherosclerosis pathology linked to systemic inflammation resulting from chronic exposure to tissue injury, infectious agents and pathogens. ..
  24. iPS-derived hepatocytes as a model of familial hypercholesterolemia
    Max A Cayo; Fiscal Year: 2013
    ..abstract_text> ..
  25. Characterization of Diet1, a hypercholesterolemia resistance gene
    Karen Reue; Fiscal Year: 2013
    ..Results will further elucidate the mechanisms that control cholesterol homeostasis, and may suggest new strategies for protection or treatment of hypercholesterolemia and related disorders. ..
  26. Plasminogen activator inhibitor-1 in tumor progression and metastasis
    Yves A DeClerck; Fiscal Year: 2013
    ....
  27. APOLIPOPROTEIN GENES AND ATHEROGENESIS IN ANIMALS
    Nobuyo Maeda; Fiscal Year: 2012
    ..Using mouse genetics as a tool, we aim to determine how some common human genetic differences affect atherosclerosis and how the genetic effects are influenced by being overweight and by other common gene variants. ..
  28. Development of Extracellular Heat Shock Protein-90 as a Novel Topical Wound Heali
    Wei Li; Fiscal Year: 2013
    ..Our goal is to develop a recombinant Hsp90a peptide into a novel and more effective wound-healing agent. ..
  29. The Effect of Diet and Nutrients on the Progression and Treatment of Prostate Can
    George Thomas; Fiscal Year: 2013
    ..Among these, obesity is an increasingly important risk factor. This project will examine the role of diet in the progression of prostate cancer and as an avenue for designing new therapeutic approaches based on existing mouse models. ..
  30. Targeting PCSK9 Transcription to Combat Hypercholesterolemia by Berberine
    Jingwen Liu; Fiscal Year: 2013
    ....
  31. NUCLEAR RECEPTOR SIGNALING PATHWAYS IN ATHEROGENESIS
    PETER J TONTONOZ; Fiscal Year: 2013
    ..We will also generate and analyze lesion formation in Idol-/- human apoBTg mice. ..
  32. Alternative Splicing in Regulation of Cholesterol Synthesis and Uptake
    Marisa Wong Medina; Fiscal Year: 2013
    ....
  33. The role of b-carotene in maternal-fetal nutrition
    Loredana Quadro; Fiscal Year: 2013
    ..These studies have a significant impact on human health, since they aim at reducing the incidence of fetal malformations associated with an abnormal maternal intake of micronutrients, such as vitamins. ..
  34. Role of Fibrinolytic System in Vein Graft Remodeling
    William P Fay; Fiscal Year: 2013
    ..We anticipate that the information gained from our experiments will lead to new strategies to treat and prevent vein graft disease. ..
  35. Molecular Basis of Autosomal Dominant Hypercholesterolemia in a Multiethnic Cohor
    Zahid Ahmad; Fiscal Year: 2013
    ..The studies outlined in this project will provide the basis for the development of new therapeutic options for the prevention of this potentially life-threatening chronic disease. ..
  36. Inflammation, Atherosclerosis and ApoA-I
    Mary G Sorci-Thomas; Fiscal Year: 2013
    ..These studies will likely provide new targets for therapeutic interventions to control the inflammatory processes that exacerbate atherosclerosis. ..
  37. Developing A Novel Therapy for Diabetic Retinopathy
    Danyang Chen; Fiscal Year: 2013
    ..The proposed studies will lay a solid groundwork for future Phase II preclinical studies of CLT-020 and this project may develop a more effective therapeutics to cure DR. ..
  38. ApoE receptor pathways and abeta metabolism
    Guojun Bu; Fiscal Year: 2013
    ..Together, our proposed studies will likely provide insight into the mechanisms underlying A[unreadable] clearance and aggregation pathways in the brain and uncover how apoE isoforms and apoE receptors regulate these events in AD. ..
  39. Macrophage, ABCA1, Inflammation, and Atherosclerosis
    John S Parks; Fiscal Year: 2012
    ..In this proposal, we seek to understand the relationship between macrophage inflammation that results from the specific deletion of a membrane cholesterol transporter on development of atherosclerosis, obesity and insulin resistance. ..
  40. An immunoadhesin for treatment of hypercholesterolemia
    KEITH WYCOFF; Fiscal Year: 2012
    ..A receptor decoy based on a protein fragment of the low-density lipoprotein receptor fused to IgG Fc is expected to dramatically lower LDL-C and reduce the risk of coronary artery disease. ..
  41. Does Diabetic Hyperglycemia Regulate Atherosclerosis Progression and Regression?
    ROBERT RAFFAI; Fiscal Year: 2013
    ..Our long-term goals are to identify mechanisms that could serve as therapeutic targets to delay the progression and accelerate the regression of atherosclerosis as treatments for PAD in diabetic individuals. ..
  42. Structure of sclerostin protein complexes
    Rajiv Kumar; Fiscal Year: 2012
    ..This effort will greatly help women and men with osteoporosis and osteoporosis-related fractures. ..
  43. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
    ..End of Abstract) ..
  44. Screens for novel compounds to correct diabetic postprandial dyslipidemia
    Kevin Jon Williams; Fiscal Year: 2011
    ..A quarter century ago, hepatic uptake of remnants was shown to be independent of LDL receptors. This realization launched a long, difficult search for the responsible molecules...
  45. Role of ERK1/2 in Neuromuscular Synapses and Myofiber Development in vivo
    Mendell Rimer; Fiscal Year: 2013
    ....
  46. MOLECULAR BASIS OF CHOLESTEROL METABOLISM
    Joseph L Goldstein; Fiscal Year: 2013
    ..heart attacks as much as 88%;3) demonstration that PCSK9 functions extracellularly to bind and degrade LDL receptors, an observation that stimulated pharmaceutical companies to develop antibodies that block PCSK9 and lower LDL;..
  47. Contribution of the LDL receptor-related protein (LRP) to inflammation and sepsis
    Eric A Williams; Fiscal Year: 2010
    ....
  48. Green Tea Nanocarriers: A Promising Approach for the Prevention and Treatment of
    Shu Wang; Fiscal Year: 2011
    ..S. and abroad. The outcome is also expected to produce dramatic savings in the cost of medical care and improve the quality of life. ..
  49. RAGE, Macrophages &HDL Biology
    Ann Marie Schmidt; Fiscal Year: 2013
    ..Taken together, this work will uncover novel therapeutic strategies to enhance HDL function and cardiovascular health. ..
  50. Sir2 Regulates AMPK and Lipid Metabolism in Diabetes
    Mengwei Zang; Fiscal Year: 2012
    ..Activation of SIRT1/AMPK signaling will provide new therapeutic targets for intervention of diabetes and its vascular complications. ..
  51. Obesity, Inflammation and BPH
    Simon W Hayward; Fiscal Year: 2013
    ..abstract_text> ..
  52. T-cell Co-stimulation in Obesity-induced Inflammation and Atherosclerosis
    Vince N Montes; Fiscal Year: 2013
    ..The research environment at the University of Washington is excellent for a budding physician- scientist, and I plan on taking absolute advantage of the resources available. (End of Abstract) ..
  53. METABOLISM OF THE VLDL RECEPTOR AND APOE RECEPTOR 2
    JOACHIM J HERZ; Fiscal Year: 2013
    ....
  54. LRP1 and endothelial function
    Xinchun Pi; Fiscal Year: 2013
    ..The knowledge gained from this proposal will provide novel therapeutic targets and strategies for treating angiogenesis-dependent diseases and atherosclerosis. ..
  55. REGULATION OF INFLAMMATION BY PULMONARY COLLECTINS
    Peter M Henson; Fiscal Year: 2012
    ....
  56. Co-infections of rhinovirus and bacteria in chronic lung disorders
    UMADEVI SIVANAPPA SAJJAN; Fiscal Year: 2010
    ..Understanding how viral infections promote bacterial colonization and infection may lead to improved treatments that prevent progression of chronic lung disease. ..
  57. Mechanisms for cell uptake of LDL/DNA complexes
    NATALIA V GUEVARA; Fiscal Year: 2013
    ..This project will advance our understanding of the natural function of LDL as nucleic acid delivery vector. ..
  58. PCSK9, Lipoprotein receptors, and Atherosclerosis
    Sergio Fazio; Fiscal Year: 2013
    ..We are proposing to investigate these correlations in detail and to evaluate the overall impact of PCSK9 expression on lipoprotein receptors and atherosclerosis. ..
  59. LDL Receptor Related Protein-1 in Metabolic and Cardiovascular Disease Modulation
    David Y Hui; Fiscal Year: 2013
    ....
  60. Cholesterol Uptake by Cryptosporidium
    Isabelle Coppens; Fiscal Year: 2010
    ..We will study the mechanisms by which the parasite scavenges host cholesterol, in order to specifically interfere with the pathogen's supply of this essential lipid, thereby causing its growth arrest through starvation. ..
  61. LRP AND ALZHEIMER'S DISEASE
    Bradley T Hyman; Fiscal Year: 2011
    ..Description, ..
  62. Development of Porcine Genetic Models of Atherosclerosis
    SCOTT CHRISTOPHER FAHRENKRUG; Fiscal Year: 2011
    ..These pigs will be further characterized on the basis of subsequent funding, and if evidence of accelerated atherosclerosis is found, a population of pigs will be generated and provided for sale to the biomedical research community. ..
  63. EFFECT OF APOLIPOPROTEIN STRUCTURAL ADAPTABILITY
    ROBERT O apos MARA RYAN; Fiscal Year: 2010
    ..Results obtained will improve understanding of how apoE regulates lipid metabolism and its association with disease susceptibility. ..
  64. APOE3 AND APOE4 EFFECTS ON CELLULAR PATHOBIOLOGY
    ROBERT PITAS; Fiscal Year: 1999
    ....
  65. Megakaryocyte Chemokines & Post-Irradiation Thrombocytopenia
    Mortimer Poncz; Fiscal Year: 2009
    ..Further, we anticipate that this strategy that blocks the described negative loop in megakaryopoiesis can be combined with other therapies, such as thrombopoietin-based therapy, to maximize therapeutic outcome after radiation exposure. ..
  66. HEPATITIS C VIRUS IN ETIOLOGY OF WA RHEUMATOID FACTORS
    Vincent Agnello; Fiscal Year: 2001
    ..The main physiologic role of WA antibodies is to block endocytosis of HCV VLDL complexes by the LDL receptors. The retarded endocytosis of HCV-VLDL complexes containing apolipoprotein E2 via the LDL receptor is the ..
  67. Molecular Mechanism of Protein Kinase Cbeta-Mediated Cholesterol Homeostasis
    Kamal D Mehta; Fiscal Year: 2010
    ..exchangeable free cholesterol, there is no information available regarding the role and regulation of adipose LDL receptors and its relationship to whole body cholesterol homeostasis...
  68. Regulation of syndecan 1 in by n-3 PUFA
    IRIS EDWARDS; Fiscal Year: 2009
    ..Since LDL receptors are upregulated in tumor cells, this pathway is likely to represent a major route for delivery of fatty acids ..
  69. Scalable Production of New Generation Adeno-Associated Virus Gene Therapy Vectors
    MARTIN W LOCK; Fiscal Year: 2010
    ..The overall goal of this project is to develop a large-scale production system for the commercial manufacture of a novel therapeutic for familial hypercholesterolemia. ..
  70. REGULATION OF LDL RECEPTORS IN ADIPOCYTES
    FREDRIC KRAEMER; Fiscal Year: 1993
    ..The first objective is to demonstrate that LDL receptors have a different subcellular localization in adipocytes than other cells; specifically, adipocytes contain a ..
  71. Copper's Role in Brain LRP-mediated Abeta Efflux and Aging
    Rashid Deane; Fiscal Year: 2010
    ..These studies may provide new therapeutic insights on how to lower brain A[unreadable] by controlling its CNS barriers transport in Cu-potentiated neurodegenerative disorders. ..
  72. MECHANISM OF APOLIPOPROTEIN B-48 BIOGENESIS
    Lawrence Chan; Fiscal Year: 1993
    ..The proposed work will shed light on this process, which also has profound implications for general cell and molecular biology...
  73. MPT INHIBITOR IND 50,820 IN FAMILIAL HYPERCHOLESTEROLEM*
    Marina Cuchel; Fiscal Year: 2009
    ..This study would serve as basis for approval of BMS-201038 for hoFH. ..
  74. HEPATIC METABOLISM OF DIET DERIVED LIPOPROTIENS
    ALLEN COOPER; Fiscal Year: 2003
    ..hypothesis to be tested is that the initial rate of chylomicron remnant removal is determined by the number of LDL receptors, and the capacity of the liver to sequester the particles before internalizing them (sequestration space)...