apolipoproteins e

Summary

Summary: Prominent protein constituents of plasma VLDL, chylomicrons, and a subfraction of HDL as well as of remnant lipoproteins which are derived from the lipoprotein lipase-mediated intravascular catabolism of triglyceride-rich lipoproteins. Apolipoproteins E are recognized by the LDL receptor and Apo E receptor. Any defect in the Apo E metabolism leads to increased plasma Apo E levels. A strong association has been found between high levels of Apo E and type III hyperlipoproteinemia.

Top Publications

  1. ncbi Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
    E H Corder
    Department of Medicine, Joseph and Kathleen Bryan Alzheimer s Disease Research Center, Duke University Medical Center, Durham, NC 27710
    Science 261:921-3. 1993
  2. 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
  3. pmc The role of apolipoprotein E in Alzheimer's disease
    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 63:287-303. 2009
  4. pmc Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
    Filip K Swirski
    Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Clin Invest 117:195-205. 2007
  5. ncbi Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium
    L A Farrer
    Department of Neurology, Boston University School of Medicine, Mass 02118, USA
    JAMA 278:1349-56. 1997
  6. ncbi Apolipoprotein E: far more than a lipid transport protein
    R W Mahley
    Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, California 94141 9100, USA
    Annu Rev Genomics Hum Genet 1:507-37. 2000
  7. pmc Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
    Guojun Bu
    Hope Center for Neurological Disorders, Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Rev Neurosci 10:333-44. 2009
  8. ncbi Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells
    A S Plump
    Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, New York 10021 6399
    Cell 71:343-53. 1992
  9. pmc ApoE promotes the proteolytic degradation of Abeta
    Qingguang Jiang
    Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Neuron 58:681-93. 2008
  10. ncbi ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree
    Y Nakashima
    Department of Pathology, University of Washington, Seattle 98195
    Arterioscler Thromb 14:133-40. 1994

Detail Information

Publications307 found, 100 shown here

  1. ncbi Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
    E H Corder
    Department of Medicine, Joseph and Kathleen Bryan Alzheimer s Disease Research Center, Duke University Medical Center, Durham, NC 27710
    Science 261:921-3. 1993
    ..Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80...
  2. 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...
  3. pmc The role of apolipoprotein E in Alzheimer's disease
    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 63:287-303. 2009
    ..Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE...
  4. pmc Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
    Filip K Swirski
    Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Clin Invest 117:195-205. 2007
    ..Conversely, the number of Ly-6C(lo) cells remained unaffected. Thus, we believe that Ly-6C(hi) monocytes represent a newly recognized component of the inflammatory response in experimental atherosclerosis...
  5. ncbi Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium
    L A Farrer
    Department of Neurology, Boston University School of Medicine, Mass 02118, USA
    JAMA 278:1349-56. 1997
    ..To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations...
  6. ncbi Apolipoprotein E: far more than a lipid transport protein
    R W Mahley
    Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, California 94141 9100, USA
    Annu Rev Genomics Hum Genet 1:507-37. 2000
    ..Functional differences in the apoE isoforms that affect (or did affect) survival before the reproductive years probably account, at least in part, for the allele frequencies of the present day...
  7. pmc Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
    Guojun Bu
    Hope Center for Neurological Disorders, Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Rev Neurosci 10:333-44. 2009
    ..Emerging knowledge of the contribution of APOE to the pathophysiology of AD presents new opportunities for AD therapy...
  8. ncbi Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells
    A S Plump
    Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, New York 10021 6399
    Cell 71:343-53. 1992
    ..apoE-deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis...
  9. pmc ApoE promotes the proteolytic degradation of Abeta
    Qingguang Jiang
    Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Neuron 58:681-93. 2008
    ..GW3965 treatment also reversed contextual memory deficits. These data demonstrate a mechanism through which ApoE facilitates the clearance of Abeta from the brain and suggest that LXR agonists may represent a novel therapy for AD...
  10. ncbi ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree
    Y Nakashima
    Department of Pathology, University of Washington, Seattle 98195
    Arterioscler Thromb 14:133-40. 1994
    ..This model should provide numerous opportunities to study the pathogenesis and therapy of atherosclerosis in a small, genetically defined animal...
  11. ncbi Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review
    June E Eichner
    Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma, Oklahoma City 73190, OK
    Am J Epidemiol 155:487-95. 2002
    ..In addition to genotype-phenotype associations with vascular disease, the alleles and isoforms of apo var epsilon have been related to dementias, most commonly Alzheimer's disease...
  12. ncbi Natural regulatory T cells control the development of atherosclerosis in mice
    Hafid Ait-Oufella
    Institut National de la Sante et de la Recherche Medicale INSERM, Unit 689, Centre de Recherché Cardiovasculaire Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France
    Nat Med 12:178-80. 2006
    ..These results provide new insights into the immunopathogenesis of atherosclerosis and could lead to new therapeutic approaches that involve immune modulation using regulatory T cells...
  13. pmc Cardiac and vascular phenotypes in the apolipoprotein E-deficient mouse
    Elisardo C Vasquez
    Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil
    J Biomed Sci 19:22. 2012
    ..In this review, we provide an overview of the cardiac and vascular phenotypes and discuss the interplay among nitric oxide, reactive oxygen species, aging and diet in the impairment of cardiovascular function in this mouse model...
  14. ncbi Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis
    L Boring
    Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141, USA
    Nature 394:894-7. 1998
    ..These data reveal a role for MCP-1 in the development of early atherosclerotic lesions and suggest that upregulation of this chemokine by minimally oxidized lipids is an important link between hyperlipidaemia and fatty streak formation...
  15. pmc Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice
    A Daugherty
    Division of Cardiovascular Medicine, Gill Heart Institute, Department of Physiology, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA
    J Clin Invest 105:1605-12. 2000
    ..These results demonstrate that increased plasma concentrations of Ang II have profound and rapid effects on vascular pathology when combined with hyperlipidemia, in the absence of hemodynamic influences...
  16. pmc Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice
    M Febbraio
    Department of Medicine, Division of Hematology and Medical Oncology, Center of Vascular Biology, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Clin Invest 105:1049-56. 2000
    ..These results support a major role for CD36 in atherosclerotic lesion development in vivo and suggest that blockade of CD36 can be protective even in more extreme proatherogenic circumstances...
  17. ncbi Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL
    X H Xu
    Atherosclerosis Research Center, Burns and Allen Research Institute, Division of Cardiology, Steven Spielberg Pediatric Research Center, Los Angeles, California, USA
    Circulation 104:3103-8. 2001
    ..Moreover, upregulation of TLR-4 in macrophages by oxidized LDL suggests that TLR-4 may provide a potential pathophysiological link between lipids and infection/inflammation and atherosclerosis...
  18. pmc Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent
    Elena Galkina
    Department of Biomedical Engineering, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA
    J Exp Med 203:1273-82. 2006
    ..Atherosclerosis induces the recruitment of macrophages and dendritic cells that support antigen presentation...
  19. ncbi Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E
    S H Zhang
    Department of Pathology, University of North Carolina, Chapel Hill 27599 7525
    Science 258:468-71. 1992
    ..The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process...
  20. ncbi Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis
    Maik Drechsler
    Institute for Molecular Cardiovascular Research, Pauwelsstrasse 30, 52074 Aachen, Germany
    Circulation 122:1837-45. 2010
    ..Here, we investigate the effect of hypercholesterolemia on peripheral neutrophil counts, neutrophil recruitment to atherosclerotic lesions, and the importance of neutrophils in atherosclerotic lesion formation in Apoe(-/-) mice...
  21. pmc Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells
    J A Piedrahita
    Department of Pathology and Curriculum in Genetics, University of North Carolina, Chapel Hill 27599 7525
    Proc Natl Acad Sci U S A 89:4471-5. 1992
    ..Mice homozygous for the disrupted gene were produced from the heterozygotes; they appear healthy, even though they have no apolipoprotein E in their plasma...
  22. ncbi Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease
    Yiqing Song
    Brigham and Women s Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts 02215, USA
    Ann Intern Med 141:137-47. 2004
    ..Despite many population studies, however, the impact of apoE polymorphism on risk for CHD remains uncertain...
  23. ncbi Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis
    Ralph Gareus
    Institute of Genetics, Centre for Molecular Medicine CMMC, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases CECAD, University of Cologne, Zülpicher Str 47, 50674 Cologne, Germany
    Cell Metab 8:372-83. 2008
    ..Thus, endothelial NF-kappaB signaling orchestrates proinflammatory gene expression at the arterial wall and promotes the pathogenesis of atherosclerosis...
  24. pmc Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
    Suzanne E Wahrle
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 118:671-82. 2008
    ..These data support the conclusions that increased ABCA1-mediated lipidation of apoE in the CNS can reduce amyloid burden and that increasing ABCA1 function may have a therapeutic effect on AD...
  25. pmc A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation
    Steffen Massberg
    Deutsches Herzzentrum und 1 Medizinische Klinik, Technische Universitat Munchen, Germany
    J Exp Med 196:887-96. 2002
    ..These findings establish the platelet as a major player in initiation of the atherogenetic process...
  26. pmc Endothelial dysfunction in the apolipoprotein E-deficient mouse: insights into the influence of diet, gender and aging
    Silvana S Meyrelles
    Departament of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil
    Lipids Health Dis 10:211. 2011
    ..Second, we discuss the main mechanisms underlying the endothelial dysfunction of conducting vessels and resistance vessels and examine how this vascular defect can be influenced by diet, aging and gender in the apoE⁻/⁻ mouse...
  27. ncbi Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model
    Li Li
    Department of Periodontology and Oral Biology, School of Dental Medicine, Boston University, Boston, Mass 02118, USA
    Circulation 105:861-7. 2002
    ....
  28. pmc Apolipoprotein E induces antiinflammatory phenotype in macrophages
    Daniel Baitsch
    Center for Laboratory Medicine, University Hospital Munster, and Leibniz Institute for Arteriosclerosis Research, University of Munster, Albert Schweizer Strasse 33, 48129 Munster, Germany
    Arterioscler Thromb Vasc Biol 31:1160-8. 2011
    ..Apolipoprotein E (apoE) exerts potent antiinflammatory effects. Here, we investigated the effect of apoE on the functional phenotype of macrophages...
  29. pmc Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort
    Li Shen
    Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 950 West Walnut Street R2 E124, Indianapolis, IN 46202, USA
    Neuroimage 53:1051-63. 2010
    ..A genome-wide, whole brain search strategy has the potential to reveal novel candidate genes and loci warranting further investigation and replication...
  30. ncbi Endothelial arginase II: a novel target for the treatment of atherosclerosis
    Sungwoo Ryoo
    Department of Anesthesiology Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
    Circ Res 102:923-32. 2008
    ..These data indicate that arginase II plays a critical role in the pathophysiology of cholesterol-mediated endothelial dysfunction and represents a novel target for therapy in atherosclerosis...
  31. pmc Role of toll-like receptor 4 in intimal foam cell accumulation in apolipoprotein E-deficient mice
    Mie Higashimori
    Tufts Medical Center, Boston, MA 02111, USA
    Arterioscler Thromb Vasc Biol 31:50-7. 2011
    ....
  32. ncbi Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease
    Suzanne E Wahrle
    Program in Neurosciences, Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:43236-42. 2005
    ..Together, these data suggest that despite substantially lower apoE levels, poorly lipidated apoE produced in the absence of ABCA1 is strongly amyloidogenic in vivo...
  33. ncbi Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain
    Veronica Hirsch-Reinshagen
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver V5Z 4H4, Canada
    J Biol Chem 279:41197-207. 2004
    ..Additionally, the effect of ABCA1 on apoE is selective, as apoJ levels are unchanged in brains of ABCA1-/- mice. Taken together, these results show that glial ABCA1 is a key influence on apoE metabolism in the CNS...
  34. pmc Human apolipoprotein e is required for infectivity and production of hepatitis C virus in cell culture
    Kyung Soo Chang
    Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    J Virol 81:13783-93. 2007
    ..Our findings also identified apoE as a novel target for discovery and development of antiviral drugs and monoclonal antibodies to suppress HCV virion formation and infection...
  35. ncbi Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging
    Joan Lindsay
    Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
    Am J Epidemiol 156:445-53. 2002
    ..The protective associations warrant further study. In particular, regular physical activity could be an important component of a preventive strategy against Alzheimer's disease and many other conditions...
  36. ncbi Plasma lipoproteins: apolipoprotein structure and function
    R W Mahley
    J Lipid Res 25:1277-94. 1984
    ....
  37. ncbi Pulmonary arterial hypertension is linked to insulin resistance and reversed by peroxisome proliferator-activated receptor-gamma activation
    Georg Hansmann
    Department of Pediatrics, Division of Pediatric Cardiology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Circulation 115:1275-84. 2007
    ..We therefore hypothesized that insulin-resistant apoE-deficient (apoE-/-) mice would develop PAH that could be reversed by a peroxisome proliferator-activated receptor-gamma agonist (eg, rosiglitazone)...
  38. pmc Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE
    Michelle N Bradley
    Howard Hughes Medical Institute and Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, California 90095 1662, USA
    J Clin Invest 117:2337-46. 2007
    ..These observations indicate that LXRalpha has an essential role in maintaining peripheral cholesterol homeostasis in the context of hypercholesterolemia and provide in vivo support for drug development strategies targeting LXRbeta...
  39. ncbi Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E
    S W Barger
    Donald W Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock 72205, USA
    Nature 388:878-81. 1997
    ..Because sAPP-beta is deficient in the neuroprotective activity shown by sAPP-alpha, our results indicate that increased amyloidogenic processing could adversely affect the balance of sAPP activities that determine neuronal viability...
  40. ncbi Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease
    Hao Li
    GlaxoSmithKline, Research Triangle Park, North Carolina, USA
    Arch Neurol 65:45-53. 2008
    ..To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs...
  41. ncbi Inhibition of IL-17A attenuates atherosclerotic lesion development in apoE-deficient mice
    Christian Erbel
    Department of Cardiology, University of Heidelberg, Heidelberg, Germany
    J Immunol 183:8167-75. 2009
    ..The present data support a pathogenic role of IL-17A in the development of atherosclerosis by way of its widespread proinflammatory and proapoptotic effects on atherogenic cells...
  42. pmc IFN-gamma potentiates atherosclerosis in ApoE knock-out mice
    S Gupta
    Department of Medicine, Columbia University, New York 10032, USA
    J Clin Invest 99:2752-61. 1997
    ..Therefore, therapeutic inhibition of IFN-gamma signaling may lead to the formation of more lipid-poor and stable atheromata...
  43. ncbi Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles
    Wagane J A Benga
    Institut National de la Santé et de la Recherche Médicale INSERM Unite 748, Strasbourg, France
    Hepatology 51:43-53. 2010
    ..The functional relevance of the apoE-NS5A interaction for production of viral particles was supported by loss or decrease of apoE-NS5A binding in assembly-defective viral mutants...
  44. pmc Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice
    Evis Harja
    Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, New York 10032, USA
    J Clin Invest 118:183-94. 2008
    ..These data highlight unifying mechanisms whereby endothelial RAGE and its ligands mediate vascular and inflammatory stresses that culminate in atherosclerosis in the vulnerable vessel wall...
  45. ncbi Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction
    Xiu Fen Ming
    Vascular Biology, Department of Medicine, Division of Physiology, University of Fribourg, Fribourg, Switzerland
    Circulation 110:3708-14. 2004
    ..This study investigated regulatory mechanisms of arginase activity in endothelial cells and its role in atherosclerosis...
  46. pmc Apolipoprotein E in Alzheimer's disease and other neurological disorders
    Philip B Verghese
    Department of Neurology, Hope Center for Neurological Disorders, and the Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA
    Lancet Neurol 10:241-52. 2011
    ..The possibility that APOE has a role in these and other neurological diseases has been of great interest, but convincing associations have not yet emerged...
  47. ncbi The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease
    Veronica Hirsch-Reinshagen
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V4Z 5H5, Canada
    J Biol Chem 280:43243-56. 2005
    ..These data suggested that ABCA1-mediated effects on apoE levels and lipidation influenced amyloidogenesis in vivo...
  48. pmc Synthetic LXR ligand inhibits the development of atherosclerosis in mice
    Sean B Joseph
    Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095 1662, USA
    Proc Natl Acad Sci U S A 99:7604-9. 2002
    ..These observations provide direct evidence for an atheroprotective effect of LXR agonists and support their further evaluation as potential modulators of human cardiovascular disease...
  49. pmc B cell depletion reduces the development of atherosclerosis in mice
    Hafid Ait-Oufella
    Institut National de la Sante et de la Recherche Medicale INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris, France
    J Exp Med 207:1579-87. 2010
    ..These results challenge the current paradigm that B cell activation plays an overall protective role in atherogenesis and identify new antiatherogenic strategies based on B cell modulation...
  50. ncbi Antagonism of RANTES receptors reduces atherosclerotic plaque formation in mice
    Niels R Veillard
    Division Cardiology, Foundation for Medical Research, University Hospital Geneva, Geneva, Switzerland
    Circ Res 94:253-61. 2004
    ..Thus, our findings indicate that blockade of chemokine receptor/ligand interactions might become a novel therapeutic strategy to reduce the evolution of this common disease...
  51. pmc Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOP
    Edward Thorp
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Cell Metab 9:474-81. 2009
    ..These data provide direct evidence for a causal link between the ER stress effector CHOP and plaque necrosis and suggest that interventions weakening this arm of the UPR may lessen plaque progression...
  52. ncbi Mouse models of atherosclerosis
    Alan Daugherty
    Gill Heart Institute, Division of Cardiovascular Medicine, University of Kentucky, Lexington 40536, USA
    Am J Med Sci 323:3-10. 2002
    ..This review selectively highlights some of the most commonly used mouse models of atherosclerosis and compare their lesions to those formed in the human disease...
  53. ncbi Diesel exhaust induces systemic lipid peroxidation and development of dysfunctional pro-oxidant and pro-inflammatory high-density lipoprotein
    Fen Yin
    Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Arterioscler Thromb Vasc Biol 33:1153-61. 2013
    ..To evaluate whether exposure to air pollutants induces oxidative modifications of plasma lipoproteins, resulting in alteration of the protective capacities of high-density lipoproteins (HDLs)...
  54. ncbi Uremia accelerates both atherosclerosis and arterial calcification in apolipoprotein E knockout mice
    Ziad A Massy
    INSERM Unit 507, Necker Hospital, 161, rue de Sèvres 75015 Paris, France
    J Am Soc Nephrol 16:109-16. 2005
    ..We anticipate that this experimental model will be useful to test treatment strategies aimed at decreasing the accelerated atherosclerosis and arterial calcification in uremia...
  55. pmc Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia
    Eric M Reiman
    Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006, USA
    Proc Natl Acad Sci U S A 101:284-9. 2004
    ..Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia...
  56. pmc fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease
    Mark W Bondi
    University of California San Diego and VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA
    Neurology 64:501-8. 2005
    ..The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults...
  57. ncbi Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice
    Radosveta Koldamova
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 280:43224-35. 2005
    ..These results suggest that ABCA1 plays a role in the pathogenesis of parenchymal and cerebrovascular amyloid pathology and thus may be considered a therapeutic target in AD...
  58. pmc Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins
    S Horkko
    Department of Medicine, University of California, San Diego, La Jolla, California 92093 0682
    J Clin Invest 103:117-28. 1999
    ....
  59. ncbi Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles
    Aldo Grefhorst
    Laboratory of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Hospital Groningen, Hanzeplein 1, 9713 RB Groningen, The Netherlands
    J Biol Chem 277:34182-90. 2002
    ..We conclude that, in addition to raising high density lipoprotein cholesterol concentrations, pharmacological LXR activation in mice leads to development of hepatic steatosis and secretion of atherogenic, large TG-rich VLDL particles...
  60. ncbi ApoE genotype accounts for the vast majority of AD risk and AD pathology
    Jacob Raber
    Departments of Behavioral Neuroscience and Neurology, L470, ONPRC, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97201, USA
    Neurobiol Aging 25:641-50. 2004
    ..Thus, the epidemiologic and basic science evidence suggest that apoE genotype accounts for the vast majority of AD risk and pathology...
  61. pmc 11β-hydroxysteroid dehydrogenase type 2 deficiency accelerates atherogenesis and causes proinflammatory changes in the endothelium in apoe-/- mice
    Graeme A Deuchar
    Centre for Cardiovascular Science, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
    Endocrinology 152:236-46. 2011
    ..Thus, loss of 11β-HSD2 leads to striking atherogenesis associated with activation of MR, stimulating proinflammatory processes in the endothelium of E/b2 mice...
  62. pmc Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease
    Carlos Fernandez-Hernando
    Department of Pharmacology and Vascular Biology and Therapeutics, Amistad Building, 10 Amistad St, Yale University School of Medicine, New Haven, CT 06511, USA
    Cell Metab 6:446-57. 2007
    ..The presence of coronary lesions in ApoE(-/-)Akt1(-/-) mice provides a new model for studying the mechanisms of acute coronary syndrome in humans...
  63. pmc HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells
    Jonathan E Feig
    The Leon H Charney Division of Cardiology, Department of Medicine, The Marc and Ruti Bell Program in Vascular Biology, New York University School of Medicine, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 108:7166-71. 2011
    ..Overall, these results establish HDL as a regulator in vivo of the migratory and inflammatory properties of monocyte-derived cells in mouse atherosclerotic plaques, and highlight the phenotypic plasticity of these cells...
  64. ncbi A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice
    Junichi Matsubara
    Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    J Am Coll Cardiol 59:265-76. 2012
    ..The aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS)...
  65. pmc Gene expression changes in foam cells and the role of chemokine receptor CCR7 during atherosclerosis regression in ApoE-deficient mice
    Eugene Trogan
    Marc and Ruti Bell Vascular Biology Program, Leon H Charney Division of Cardiology Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 103:3781-6. 2006
    ..Taken with the other gene expression data, these results in vivo point to complex relationships among the immune system, nuclear hormone receptors, and inflammation during regression...
  66. ncbi Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice
    Z Mallat
    Institut National de la Sante et de la Recherche Medicale, INSERM U541, France
    Circ Res 89:930-4. 2001
    ..Moreover, inhibition of TGF-beta signaling favors the development of lesions with increased inflammatory component and decreased collagen content. These results identify a major protective role for TGF-beta in atherosclerosis...
  67. ncbi Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis
    Murray C H Clarke
    Division of Cardiovascular Medicine, University of Cambridge, Box 110, ACCI, Addenbrooke s Hospital, Cambridge, CB2 2QQ, UK
    Nat Med 12:1075-80. 2006
    ..In contrast, VSMC apoptosis alone is sufficient to induce features of plaque vulnerability in atherosclerosis. SM22alpha-hDTR Apoe-/- mice may represent an important new model to test agents proposed to stabilize atherosclerotic plaques...
  68. ncbi ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE
    Suzanne E Wahrle
    Program in Neurosciences, Washington University, St Louis, Missouri 63110, USA
    J Biol Chem 279:40987-93. 2004
    ..Since apoE isoforms and levels strongly influence Alzheimer's disease pathology and risk, these data suggest that ABCA1 may be a novel therapeutic target...
  69. pmc Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system
    Robert D Bell
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Cereb Blood Flow Metab 27:909-18. 2007
    ..7-fold, whereas Abeta42 binding to apoJ enhanced Abeta42 BBB clearance rate by 83%. Thus, Abeta, apoE, and apoJ are cleared from brain by different transport pathways, and apoE and apoJ may critically modify Abeta clearance at the BBB...
  70. ncbi Apolipoprotein E structure: insights into function
    Danny M Hatters
    Gladstone Institute of Neurological Disease and Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA
    Trends Biochem Sci 31:445-54. 2006
    ..Because the function of apoE is dictated by its structure, understanding the structural properties of apoE and its isoforms is required both to determine its role in disease and for the development of therapeutic strategies...
  71. ncbi Systemic tumor necrosis factor-related apoptosis-inducing ligand delivery shows antiatherosclerotic activity in apolipoprotein E-null diabetic mice
    Paola Secchiero
    Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy
    Circulation 114:1522-30. 2006
    ....
  72. pmc Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort
    S Kim
    Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 950 West Walnut Street, R2 E124, Indianapolis, IN 46202, USA
    Neurology 76:69-79. 2011
    ..We report a genome-wide association study (GWAS) of CSF biomarkers (Aβ1-42, t-tau, p-tau181p, p-tau181p/Aβ1-42, and t-tau/Aβ1-42)...
  73. ncbi Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias
    B L Plassman
    Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
    Neurology 55:1158-66. 2000
    ..The association between antecedent head injury and AD is inconsistent...
  74. ncbi Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis
    P M Sullivan
    Department of Pathology and Laboratory of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599 7525, USA
    J Biol Chem 272:17972-80. 1997
    ..Thus the structural differences between human APOE3 and mouse ApoE proteins are sufficient to cause an increased susceptibility to dietary-induced hypercholesterolemia and atherosclerosis in the 3/3 mice...
  75. ncbi Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice
    Frank C Gibson
    Department of Medicine, Section of Infectious Diseases, Boston University Medical Center, Boston, Mass, USA
    Circulation 109:2801-6. 2004
    ..Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD...
  76. pmc Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice
    Faith M Harris
    Gladstone Institute of Neurological Disease, San Francisco, CA 94141 9100, USA
    Proc Natl Acad Sci U S A 100:10966-71. 2003
    ..Inhibiting their formation might inhibit apoE4-associated neuronal deficits...
  77. ncbi Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice
    Kiran Saraff
    Division of Cardiovascular Medicine, Gill Heart Institute, Lexington, KY, USA
    Arterioscler Thromb Vasc Biol 23:1621-6. 2003
    ....
  78. ncbi Mouse models of experimental atherosclerosis
    J Jawien
    Department of Pharmacology, Jagiellonian University School of Medicine, Krakow, Poland
    J Physiol Pharmacol 55:503-17. 2004
    ..The creation of apoE -- knockout mice has changed the face of atherosclerosis research...
  79. ncbi Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis
    Alma Zernecke
    Institute for Molecular Cardiovascular Research, Rheinisch Westfalische Technische Hochschule, Aachen University, Germany
    Circ Res 102:209-17. 2008
    ..Disrupting Cxcl12/Cxcr4 thus promotes lesion formation through deranged neutrophil homeostasis, indicating that Cxcl12/Cxcr4 controls the important contribution of neutrophils to atherogenesis in mice...
  80. pmc Does apolipoprotein E polymorphism influence susceptibility to malaria?
    M A Wozniak
    Molecular Neurobiology Laboratory, Department of Optometry and Neuroscience, UMIST, Manchester, UK
    J Med Genet 40:348-51. 2003
    ..Parasite densities, all of which were low, did not differ significantly. This effect, although based on small numbers, suggests that APOE epsilon 2 may be a risk factor for early infection...
  81. ncbi Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice
    Walter J Brecht
    Gladstone Institute of Neurological Disease, San Francisco, California 94141 9100, USA
    J Neurosci 24:2527-34. 2004
    ..Neuron-specific proteolytic cleavage of apoE4 is associated with increased phosphorylation of tau and may play a key role in the development of AD-related neuronal deficits...
  82. pmc Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice
    Leandro C F Lima
    Laboratory of Transgenes and Cardiovascular Control, Department Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil
    Lipids Health Dis 11:96. 2012
    ..The aim of this study was to investigate the effects of mononuclear cell (MNC) therapy in situ on carotid cuff-induced occlusive thrombus in the apolipoprotein E knockout (apoE-/-) mouse...
  83. pmc Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides
    T Tokuda
    Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Biochem J 348:359-65. 2000
    ....
  84. pmc TGF-[beta]1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice
    Andrew D Frutkin
    Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195 7710, USA
    Arterioscler Thromb Vasc Biol 29:1251-7. 2009
    ..The role of TGF-beta1 in aneurysm formation is also controversial. We tested whether overexpression of active TGF-beta1 in hyperlipidemic mice affects atherogenesis and aortic dilation...
  85. ncbi The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with age-related macular degeneration
    Paul N Baird
    Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia
    Invest Ophthalmol Vis Sci 45:1311-5. 2004
    ..However, not all apoE studies have found an association, and among these the associations differ. The current study was conducted to investigate further the association of this gene in AMD...
  86. pmc An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease
    Allen D Roses
    Department of Neurobiology and Neurology and the Deane Drug Discovery Institute, Duke University, Durham, North Carolina 27708, USA
    Arch Neurol 67:536-41. 2010
    ..Additional data will further refine the relationship between the length of the poly-T alleles and age at disease onset and determine if the relationship is linear...
  87. pmc ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice
    Andrew J Murphy
    Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA
    J Clin Invest 121:4138-49. 2011
    ..Although endogenous apoA-I was ineffective, pharmacologic approaches to increasing cholesterol efflux suppressed stem cell proliferative responses...
  88. pmc Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender
    Thiago M C Pereira
    Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Health Sciences Center, Federal University of EspÃrito Santo, Av Marechal Campos 1468, Vitoria, ES 29043 900, Brazil
    Lipids Health Dis 9:87. 2010
    ..Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice...
  89. ncbi Differential effects of the APOE genotype on brain function across the lifespan
    N Filippini
    University Department of Psychiatry, University of Oxford, Oxford, UK
    Neuroimage 54:602-10. 2011
    ..The APOE genotype determines age-related changes in brain function that may reflect the increased vulnerability of ε4-carriers to late-life pathology or cognitive decline...
  90. ncbi Induction of rapid atherogenesis by perivascular carotid collar placement in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice
    J H von der Thüsen
    Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden University, Leiden, The Netherlands
    Circulation 103:1164-70. 2001
    ..In mice, however, atherosclerosis-like lesions have thus far not been obtained by this method. The aim of this study was the development of a mouse model of rapid, site-controlled atherogenesis...
  91. pmc Hybrid in vivo FMT-CT imaging of protease activity in atherosclerosis with customized nanosensors
    Matthias Nahrendorf
    Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    Arterioscler Thromb Vasc Biol 29:1444-51. 2009
    ....
  92. pmc Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of amyloid-β amyloidosis
    Jungsu Kim
    Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, Knight Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 31:18007-12. 2011
    ....
  93. pmc Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice
    Yanhua Hu
    Department of Cardiac and Vascular Sciences, St George s Hospital Medical School, London, United Kingdom
    J Clin Invest 113:1258-65. 2004
    ..Our findings indicate that ex vivo expansion of these progenitor cells may have implications for cellular, genetic, and tissue engineering approaches to vascular disease...
  94. ncbi Chronic apoptosis of vascular smooth muscle cells accelerates atherosclerosis and promotes calcification and medial degeneration
    Murray C H Clarke
    University of Cambridge, Division of Cardiovascular Medicine, Addenbrooke s Hospital, Cambridge, United Kingdom
    Circ Res 102:1529-38. 2008
    ..We conclude that VSMC apoptosis is sufficient to accelerate atherosclerosis, promote plaque calcification and medial degeneration, prevent expansive remodeling, and promote stenosis in atherosclerosis...
  95. ncbi A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease
    Keith D Coon
    Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Ariz 85004, USA
    J Clin Psychiatry 68:613-8. 2007
    ....
  96. ncbi Apolipoprotein E modulates clearance of apoptotic bodies in vitro and in vivo, resulting in a systemic proinflammatory state in apolipoprotein E-deficient mice
    David J Grainger
    Department of Medicine, Addenbrooke s Hospital, University of Cambridge, Hills Road, Cambridge CB2 2QQ, United Kingdom
    J Immunol 173:6366-75. 2004
    ..Any similar reduction of apoE activity in humans may contribute to the pathogenesis of a wide range of chronic diseases including atherosclerosis, dementia, and osteoporosis...
  97. ncbi Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress
    Karen S Meir
    Department of Pathology, Hadassah University Hospital, Kiryat Hadassah, Jerusalem, Israel
    Arterioscler Thromb Vasc Biol 24:1006-14. 2004
    ..This review will examine our present understanding of the pathology and progression of plaques in this animal and highlight some of the nutritional, pharmacological, and genetic studies that have enhanced this understanding...
  98. ncbi Marked regional differences of brain human apolipoprotein E expression in targeted replacement mice
    P M Sullivan
    Bryan Alzheimer s Disease Research Center and Division of Neurology, Department of Medicine, Duke University Medical Center, Box 2900, Durham, NC 27710, USA
    Neuroscience 124:725-33. 2004
    ..Finally, the differences in apoE levels we observed may explain the regional vulnerability of neuronal degeneration in Alzheimer's disease...
  99. pmc APOE genotype-specific differences in the innate immune response
    Michael P Vitek
    Duke University Medical Center, Durham, NC 27710, USA
    Neurobiol Aging 30:1350-60. 2009
    ..Overall, these data emphasize the important role of apolipoprotein E and of the APOE genotype on the immune responses that are evident in most, if not all, neurological disease...
  100. ncbi Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriers
    Johanna Lind
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N 8, Stockholm, Sweden
    Brain 129:1240-8. 2006
    ..Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level...
  101. ncbi Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice
    Rory R Koenen
    Institute for Cardiovascular Molecular Research, Medical Faculty, RWTH Aachen University, Aachen, Germany
    Nat Med 15:97-103. 2009
    ..These results establish the in vivo relevance of chemokine heteromers and show the potential of targeting heteromer formation to achieve therapeutic effects...

Research Grants76

  1. Cross-talk Between Coagulation, Inflammation, and Immunity
    Lawrence L Leung; Fiscal Year: 2013
    ..We believe that this crosstalk between blood clotting, inflammation and immunity is important and highly relevant to our understanding of many diseases including cancer, inflammatory diseases, and abnormal blood clotting. ..
  2. Comprehensive biomarker study to capitalize on existing GWAS in 10K South Asians
    Danish Saleheen; Fiscal Year: 2010
    ..We seek support for additional blood markers to PROMIS by assaying plasma biomarkers potentially relevant to atherogenesis, plaque rupture and/or thrombosis. ..
  3. Response to and signals of caloric restriction and intermittent feeding regimens
    MARC KOPEL HELLERSTEIN; Fiscal Year: 2010
    ....
  4. Molecular Mechanism of Protein Kinase Cbeta-Mediated Cholesterol Homeostasis
    Kamal D Mehta; Fiscal Year: 2010
    ..The greatest potential for arresting this epidemic is likely to come through a clearer understanding of its molecular pathogenesis to develop rational and mechanism based therapy. ..
  5. Early Life Conditions, Survival, and Health: A Pedigree-Based Population Study
    Ken R Smith; Fiscal Year: 2013
    ..We also test if there is effect modification of APOE alleles on the association between ELCS &later-life biomarkers. ..
  6. The Role of Vascular MR-Regulated Genes in Vascular Function and Disease
    Iris Z Jaffe; Fiscal Year: 2013
    ..abstract_text> ..
  7. Transplacental Arsenic Induced Hepatic Dysfunction and Vascular Disease
    J Christopher States; Fiscal Year: 2010
    ..This project uses a mouse model of fetal arsenic exposure induced vascular disease to investigate effects of fetal arsenic exposure on liver development that likely cause vascular disease by young adulthood. ..
  8. Cholesterol and Lymphatic Transport of Molecules and Cells
    Melody A Swartz; Fiscal Year: 2012
    ..Several promising tools that may ultimately lead to valuable insight into how lymphatic disorders could be treated will be explored in this proposal. ..
  9. Epistasis in Steroidogenic Genes in the Prediction of Alzheimer's Disease
    CRAIG STEPHEN ATWOOD; Fiscal Year: 2013
    ..Successful completion of these studies would enable the development of prognostic and diagnostic tests for AD, and provide insights into the neuroendocrine mechanisms of AD. ..
  10. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
    ....
  11. CHEMOSENSORY PERCEPTION AND PSYCHOPHYSICS IN THE AGED
    CLAIRE L MURPHY; Fiscal Year: 2013
    ..2005). Elucidation of age-related changes in brain response to appetitive chemosensory stimuli may suggest avenues to modulate food intake and obesity in middle age, and metabolic disease and cognitive impairment in older adults. ..
  12. Inducible Macrophage Specific Gene Expression in Diseases
    JEANINE M D apos ARMIENTO; Fiscal Year: 2010
    ..We will also examine the consequences of the absence of macrophage tissue inhibitor of metalloproteinases-3 in lung injury. ..
  13. 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. ..
  14. THE ROLE OF A-BETA SPECIES IN VASCULAR SMOOTH MUSCLE CELL AND CEREBRAL ARTERIOLE
    Gregory J Zipfel; Fiscal Year: 2013
    ..If successful, the results of the project may point to ways to develop effective treatments to prevent or reverse the memory problems of patients with Alzheimer's Disease in the future. ..
  15. Atherogenic mechanism of lipid peroxidation-derived aldehydes
    Sanjay Srivastava; Fiscal Year: 2013
    ..Results obtained from this project will help in developing a better understanding, and potentially, novel therapeutic strategies for decreasing or managing atherosclerosis. ..
  16. Selective Insulin Resistance- Diabetic Cardiovascular Diseases
    George L King; Fiscal Year: 2013
    ....
  17. 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. ..
  18. Retinal Imaging of Prognostic Indicators of Atherosclerosis
    Frederick R Haselton; Fiscal Year: 2010
    ..Proven biomarker correlates will then be imaged in vivo in a mouse model of atherosclerosis to validate the utility of our imaging approach. ..
  19. Longitudinal Study of Lipids and APOE in the Development of AD and AD Pathology
    Michelle M Mielke; Fiscal Year: 2013
    ....
  20. ENHANCEMENT OF CORONARY CONSTRICTION BY COMBUSTION-SOURCE AIR TOXICS
    Matthew J Campen; Fiscal Year: 2012
    ..Results from these studies will assist in the assessment and management of personal risk of health effects from air pollution exposure. ..
  21. Exploring Human-Induced Pluripotent Stem Cells for Alzheimer's Disease Research
    Kuo Fen Lee; Fiscal Year: 2012
    ..Ultimately, we aim to develop genetic or chemical treatments that disrupt molecular pathways that lead to AD. ..
  22. Angiotensin II uncoupling of eNOS in hypertension
    HUA LINDA CAI; Fiscal Year: 2013
    ....
  23. Neurorestorative Strategy for Diabetic Peripheral Neuropathy
    Feng Qiao Li; Fiscal Year: 2013
    ..2) To determine if COG112 exerts neuroprotective and neurorestorative effects in vivo by functional and histological examination in a DPN model of BKS db/db mice. ..
  24. Prenatal stress and accelerated atherosclerosis in ApoE knockout mice
    Subeena Sood; Fiscal Year: 2012
    ..Identifying the genes and pathways through which prenatal stress impacts human disease will provide opportunities for treatment or prevention of these effects in adulthood. ..
  25. 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. ..
  26. Subtype Specific LXR Activity Limits Atherosclerosis
    Ira G Schulman; Fiscal Year: 2013
    ..The results of these studies should provide innovative strategies for the development of therapies for the treatment of cardiovascular disease. ..
  27. Purinergic signaling in sleep apnea
    Elzbieta Kaczmarek; Fiscal Year: 2012
    ..We suggest that P2 receptors are a promising target for the protection of vasculature from oxidative stress and inflammation, such as those observed in OSA. ..
  28. Calcification and Vascular Cell Differentiation
    Cecilia M Giachelli; Fiscal Year: 2013
    ....
  29. 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. ..
  30. Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies
    JAMES WAVELL AIKEN; Fiscal Year: 2011
    ....
  31. Multifunctional nanoformulations for diagnostic imaging of atherosclerosis
    Alexander B Sigalov; Fiscal Year: 2012
    ....
  32. Outcomes and Predictors in Mild Cognitive Impairment
    Mary Ganguli; Fiscal Year: 2012
    ..The Awardee will also continue to organize trainee workshops in neglected areas such as project management, principles of neuropsvcholoav for non-psvcholoaists. and scientific writing skills. ..
  33. FUNCTIONAL HIERARCHY OF REMNANT LIPOPROTEIN RECEPTORS
    Sergio Fazio; Fiscal Year: 2013
    ..We strive to understand the factors that regulate bulk plaque regression. ..
  34. Disordered Cellular Cholesterol Movement, Cell Death, and Multisystem Disease
    STEPHEN DEAN TURLEY; Fiscal Year: 2013
    ....
  35. Serum amyloid P and chronic noncommunicable diseases
    Weibin Shi; Fiscal Year: 2010
    ..The proposed research offers an opportunity to assess the contribution of serum amyloid P to the development of chronic noncommunicable diseases. ..
  36. Novel mechanisms by which aspirin might protect against atherosclerosis
    Sampath Parthasarathy; Fiscal Year: 2012
    ..In this application, we propose that the actions of aspirin might be mediated by salicylate. We also explore the mechanisms by which PON 1 could be induced by aspirin. ..
  37. Novel mouse models of inflammation-resolution
    Paul L Fox; Fiscal Year: 2010
    ..These models may reveal alternative targets for novel anti-inflammatory therapeutic strategies that, because of their specificity, may exhibit minimal adverse side-effects. ..
  38. Molecular Pathogenesis of Chronic Kidney Disease-Dependent Vascular Calcification
    Makoto Miyazaki; Fiscal Year: 2013
    ..Specific Aim 3: Elucidate molecular mechanisms by which ATF4 regulates osteoblastic differentiation and mineralization of VSMCs. ..
  39. Periodontal Pathogens and Cardiovascular Disease
    KESAVALU NAIDU LAKSHMYYA; Fiscal Year: 2013
    ..There is strong clinical and epidemiological association between periodontal disease and cardiovascular disease. ..
  40. High Throughput Screen for Novel Anti-Rheumatic Compounds
    Dale J Christensen; Fiscal Year: 2010
    ..In this we propose to develop assays that will help to identify these novel drug leads that can be used to develop a new anti-RA therapy. ..
  41. Endoplasmic reticulum stress and foam cell formation
    Zhongmao Guo; Fiscal Year: 2010
    ..Finding from this work should contribute to understanding of the molecular mechanism of foam cell formation, and provide strategies for treatment or prevention of atherosclerosis by inhibition of endoplasmic reticulum stress. ..
  42. 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. ..
  43. Lipoproteins and Microbial Immunity
    HOBART WHITAKER HARRIS; Fiscal Year: 2013
    ....
  44. Role of LXR and ABCA1 in Abeta Aggregation and Toxicity
    NICHOLAS FRANCIS FITZ; Fiscal Year: 2012
    ..Better understanding the role of cholesterol metabolism in AD pathology will help develop new routes of treatment to slow disease progression. ..
  45. Lipid genotypes, phenotypes, and colorectal adenomas: Elucidating mechanisms
    Polly A Newcomb; Fiscal Year: 2013
    ..Understanding how lipid genes influence adenoma risk may inform mechanisms of carcinogenesis, ultimately helping to reduce the burden of CRC. ..
  46. Epigenomic Characterization of Alzheimer's Disease Neurons from iPSCs
    Li Huei Tsai; Fiscal Year: 2012
    ....
  47. Underlying Mechanisms of ApoE in HCV Infection and Assembly
    GUANGXIANG GEORGE LUO; Fiscal Year: 2013
    ..The studies described in this application will also provide novel targets for anti-HCV drug discovery. ..
  48. Ozone, apoE4, aging, and Alzheimer's disease
    Rui Ming Liu; Fiscal Year: 2013
    ..The results will have major impact in the field and may lead to the development of novel strategies for the prevention and treatment of AD. ..
  49. Tobacco Products and Atherosclerotic Disease
    Sanjay Srivastava; Fiscal Year: 2013
    ..PHS 398/2590 (Rev. 06/09) Page Continuation Format Page ..
  50. Myeloid cell interactions with T cells in atherosclerosis
    Klaus F Ley; Fiscal Year: 2013
    ..PF4 or other molecules investigated here may emerge as targets for prevention or therapy of atherosclerosis and its complications. ..
  51. Oxidative Stress and Vascular Smoth Muscle Cell Growth
    Bradford C Berk; Fiscal Year: 2013
    ..Elucidating the tissue- and cell-specific pathways by which cyclophilin A modulates atherogenesis would provide insights for therapies to improve vascular function in this disease. ..
  52. Glucose Metabolic, Amyloid, and Tau Brain Imaging in Down's Syndrome and Dementia
    GARY WILLIAM SMALL; Fiscal Year: 2013
    ..Given the many people suffering from these neurodegenerative diseases, the potential impact of this study will be considerable, possibly improving the quality of life for millions of patients and their families. ..
  53. Selenium, other risk factors and cognitive decline in rural elderly Chinese
    Sujuan Gao; Fiscal Year: 2013
    ....
  54. 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. ..
  55. PHOSPHORYLATION AND ENDOTHELIAL NITRIC OXIDE PRODUCTION
    William C Sessa; Fiscal Year: 2013
    ....
  56. Diverse Roles of Reactive Oxygen Species and Inflammation in Vascular Disease
    Kathy K Griendling; Fiscal Year: 2013
    ..Ultimately, this research may establish new unifying concepts linking conditions that alter vascular oxidant stress and inflammation to the molecular processes underlying vasculopathies. (End of Abstract) ..
  57. Endothelial NOS by protein to protein interactions
    William C Sessa; Fiscal Year: 2013
    ..Research supported by this grant may help identify new drugs that reduce heart disease and improve the quality of life of people suffering with cardiovascular disease. ..
  58. Oxysterols, Estrogen Receptor Antagonism, and Vascular Disease
    Philip W Shaul; Fiscal Year: 2013
    ..By accomplishing these aims, we will increase our basic understanding of the biology of the only known endogenous SERM in the context of vascular health and disease. ..
  59. 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. ..
  60. GPCR Kinase-2 in TNFalpha Signaling in Macrophages
    Narayanan Parameswaran; Fiscal Year: 2013
    ..Taken together, our studies should provide important insight into the mechanisms of TNF signaling in macrophages as well as identify potential therapeutic targets in the treatment of chronic inflammatory diseases. ..
  61. Functional Analysis of ACAT
    Ta Yuan Chang; Fiscal Year: 2013
    ..The outcome of this application will help investigators to design ACAT1-specific inhibitors with minimal side effects, and help to determine the utility of ACAT1 as a target for treating atherosclerosis. ..
  62. FLUID SHEAR STRESS SIGNAL TRANSDUCTION IN ENDOTHELIUM
    Keigi Fujiwara; Fiscal Year: 2013
    ..Elucidating the specific pathways by which protein kinase C-zeta modulates vessel function would provide the basis to develop new therapies to prevent atherosclerosis. ..
  63. Therapeutic for Intracerebral Hemorrhage
    Dale Christensen; Fiscal Year: 2009
    ....
  64. Long Term Outcomes in ICU Patients: Delirium & Apolipoprotein E
    Sheila Alexander; Fiscal Year: 2009
    ..This would likely lead to decreased time in the ICU and hospital. ..
  65. Activators of the Pyrophosphatase Activity of Alkaline Phosphatase
    Jose Luis Millan; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  66. 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. ..
  67. APOE3 AND APOE4 EFFECTS ON CELLULAR PATHOBIOLOGY
    ROBERT PITAS; Fiscal Year: 1999
    ....
  68. Amyloid Beta-Protein: ApoE and Cholesterol Homeostasis
    WELLINGTON WOOD; Fiscal Year: 2009
    ..Determine if the neuronal apoE4 and apoE-null phenotype can be "rescued" by incubation with astrocytes of apoE2, apoE3, or wildtype mice. In some experiments astrocytes will be treated with ABeta1-42. ..
  69. Ocular HSV-Latency, Reactivation, and Recurrence
    James M Hill; Fiscal Year: 2012
    ..The use of two receptor-based ApoE mimetic peptides that exhibit potent anti-viral and anti-inflammatory activity, and which act to suppress this gene, holds great promise as a new therapy for ocular and other HSV-related diseases. ..
  70. A novel peptide therapy for treatment of herpetic stromal keratitis
    Partha S Bhattacharjee; Fiscal Year: 2010
    ..We propose to investigate the effectiveness of two small peptides for their anti-viral and anti-inflammatory properties for the treatment of HSK. ..
  71. APOLIPOPROTEIN E AND THE ISCHEMIC BRAIN
    David Warner; Fiscal Year: 2001
    ..We believe that this information would be of substantial value in defining both the relevance of Apo E mechanisms to ischemic outcome and provide a basis for therapeutic approaches to the treatment of stroke. ..
  72. APOE and Brain Injury in Premies
    James A Blackman; Fiscal Year: 2010
    ..If so, this could lead to a clinical trial of administration of an e4 protein isoform in the acute setting. Success in such a trial could provide a radically new and innovative approach to acute treatment of BI in newborns. ..
  73. ApoE and ApoE receptors in the molecular mechanisms of synapse formation
    HYANG HOE; Fiscal Year: 2009
    ....
  74. Apolipoprotein E Genotype and Cognitive Performance in Breast Cancer Survivors
    Brent Small; Fiscal Year: 2007
    ..In the current proposal, we examine the potential of APOE-e4 genotype, known risk factor for Alzheimer's disease, to predispose breast cancer survivors for poor cognitive outcomes. [unreadable] [unreadable] [unreadable]..
  75. HEPATIC METABOLISM OF DIET DERIVED LIPOPROTIENS
    ALLEN COOPER; Fiscal Year: 2003
    ..Together, it is anticipated that these studies will provide a concrete model for remnant removal, as well as identify the key elements in this mechanism, at which therapeutic intervention might be directed. ..
  76. APOLIPOPROTEIN E IN CHOLESTEROL TRANSPORT AND METABOLISM
    ROBERT PITAS; Fiscal Year: 1992
    ..Together, these studies will help elucidate the role of apo-E in normal nervous tissue and in nerve regeneration...