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Ceacam1 deletion causes vascular alterations in large vessels

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dc.contributor.author Najjar S.M.
dc.contributor.author Ledford K.J.
dc.contributor.author Abdallah S.L.
dc.contributor.author Paus A.
dc.contributor.author Russo L.
dc.contributor.author Kaw M.K.
dc.contributor.author Ramakrishnan S.K.
dc.contributor.author Muturi H.T.
dc.contributor.author Raphael C.K.
dc.contributor.author Lester S.G.
dc.contributor.author Heinrich G.
dc.contributor.author Pierre S.V.
dc.contributor.author Benndorf R.
dc.contributor.author Kleff V.
dc.contributor.author Jaffa A.A.
dc.contributor.author Levy E.
dc.contributor.author Vazquez G.
dc.contributor.author Goldberg I.J.
dc.contributor.author Beauchemin N.
dc.contributor.author Scalia R.
dc.contributor.author Er
dc.contributor.editor
dc.date May-2013
dc.date.accessioned 2017-10-05T15:30:57Z
dc.date.available 2017-10-05T15:30:57Z
dc.date.issued 2013
dc.identifier 10.1152/ajpendo.00266.2013
dc.identifier.isbn
dc.identifier.issn 01931849
dc.identifier.uri http://hdl.handle.net/10938/15300
dc.description.abstract Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance and endothelial survival. However, its role in the morphology of macrovessels remains unknown. Mice lacking Ceacam1 (Cc1---) exhibit hyperinsulinemia, which causes insulin resistance and fatty liver. With increasing evidence of an association among hyperinsulinemia, fatty liver disease, and atherosclerosis, we investigated whether Cc1--- exhibited vascular lesions in atherogenicprone aortae. Histological analysis revealed impaired endothelial integrity with restricted fat deposition and aortic plaque-like lesions in Cc1--- aortae, likely owing to their limited lipidemia. Immunohistochemical analysis indicated macrophage deposition, and in vitro studies showed increased leukocyte adhesion to aortic wall, mediated in part by elevation in vascular cell adhesion molecule 1 levels. Basal aortic eNOS protein and NO content were reduced, in parallel with reduced Akt-eNOS and Akt-Foxo1 phosphorylation. Ligand-induced vasorelaxation was compromised in aortic rings. Increased NADPH oxidase activity and plasma 8-isoprostane levels revealed oxidative stress and lipid peroxidation in Cc1--- aortae. siRNA-mediated CEACAM1 knockdown in bovine aortic endothelial cells adversely affected insulin's stimulation of IRS-1-PI 3-kinase-Akt-eNOS activation by increasing IRS-1 binding to SHP2 phosphatase. This demonstrates that CEACAM1 regulates both endothelial cell autonomous and nonautonomous mechanisms involved in vascular morphology and NO production in aortae. Systemic factors such as hyperinsulinemia could contribute to the pathogenesis of these vascular abnormalities. Cc1--- mice provide a first in vivo demonstration of distinct CEACAM1-dependent hepatic insulin clearance linking hepatic to macrovascular abnormalities. © 2013 the American Physiological Society.
dc.format.extent
dc.language English
dc.publisher BETHESDA
dc.relation.ispartof Publication Name: American Journal of Physiology - Endocrinology and Metabolism; Publication Year: 2013; Volume: 305; no. 4;
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Ceacam1 deletion causes vascular alterations in large vessels
dc.type Article
dc.contributor.affiliation Najjar, S.M., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Ledford, K.J., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Abdallah, S.L., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Paus, A., Institute of Anatomy, University of Duisburg, Essen, Germany
dc.contributor.affiliation Russo, L., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Kaw, M.K., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Ramakrishnan, S.K., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Muturi, H.T., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Raphael, C.K., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Lester, S.G., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Heinrich, G., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Pierre, S.V., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Benndorf, R., Institute of Anatomy and Cell Biology of Julius-Maximilians, University of Würzburg, Würzburg, Germany
dc.contributor.affiliation Kleff, V., Institute of Anatomy, University of Duisburg, Essen, Germany
dc.contributor.affiliation Jaffa, A.A., Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Lévy, E., Department of Nutrition, Research Centre, Ste-Justine Hospital, University of Montreal, Montreal, QC, Canada
dc.contributor.affiliation Vazquez, G., Center for Diabetes and Endocrine Research, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States, Department of Physiology and Pharmacology, College of Medicine and life Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States
dc.contributor.affiliation Goldberg, I.J., Division of Preventive Medicine and Nutrition, Columbia University, New York, NY, United States
dc.contributor.affiliation Beauchemin, N., Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada
dc.contributor.affiliation Scalia, R., Department of Physiology and Cardiovascular Research Center, School of Medicine, Temple University, Philadelphia, PA, United States
dc.contributor.affiliation Ergün, S., Institute of Anatomy, University of Duisburg, Essen, Germany, Institute of Anatomy and Cell Biology of Julius-Maximilians, University of Würzburg, Würzburg, Germany
dc.contributor.authorAddress Najjar, S. M.; Univ. of Toledo College of Medicine, 3000 Arlington Ave., Mail Stop 1009, Toledo, OH 43614, United States; email: sonia.najjar@utoledo.edu
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Biochemistry and Molecular Genetics;
dc.contributor.authorDepartment Biochemistry and Molecular Genetics
dc.contributor.authorDivision
dc.contributor.authorEmail sonia.najjar@utoledo.edu
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials Najjar, SM
dc.contributor.authorInitials Ledford, KJ
dc.contributor.authorInitials Abdallah, SL
dc.contributor.authorInitials Paus, A
dc.contributor.authorInitials Russo, L
dc.contributor.authorInitials Kaw, MK
dc.contributor.authorInitials Ramakrishnan, SK
dc.contributor.authorInitials Muturi, HT
dc.contributor.authorInitials Raphael, CK
dc.contributor.authorInitials Lester, SG
dc.contributor.authorInitials Heinrich, G
dc.contributor.authorInitials Pierre, SV
dc.contributor.authorInitials Benndorf, R
dc.contributor.authorInitials Kleff, V
dc.contributor.authorInitials Jaffa, AA
dc.contributor.authorInitials Levy, E
dc.contributor.authorInitials Vazquez, G
dc.contributor.authorInitials Goldberg, IJ
dc.contributor.authorInitials Beauchemin, N
dc.contributor.authorInitials Scalia, R
dc.contributor.authorInitials Ergun, S
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress Najjar, SM (reprint author), Univ Toledo, Coll Med, 3000 Arlington Ave,Mail Stop 1009, Toledo, OH 43614 USA.
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.identifier.articleNo
dc.identifier.coden AJPMD
dc.identifier.pubmedID 23800882
dc.identifier.scopusID 84881632578
dc.identifier.url
dc.publisher.address 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
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dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency R01 DK-054254, NIH, National Institutes of Health
dc.relation.ispartofFundingAgency R01 DK-083850, NIH, National Institutes of Health
dc.relation.ispartofFundingAgency R01 HL-112248, NIH, National Institutes of Health
dc.relation.ispartOfISOAbbr Am. J. Physiol.-Endocrinol. Metab.
dc.relation.ispartOfIssue 4
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle American Journal of Physiology - Endocrinology and Metabolism
dc.relation.ispartofPubTitleAbbr Am. J. Physiol. Endocrinol. Metab.
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 305
dc.source.ID WOS:000323432000006
dc.type.publication Journal
dc.subject.otherAuthKeyword Fatty liver disease
dc.subject.otherAuthKeyword Metabolic syndrome
dc.subject.otherAuthKeyword NEFA
dc.subject.otherAuthKeyword Obesity
dc.subject.otherChemCAS endothelial nitric oxide synthase, 503473-02-7
dc.subject.otherChemCAS fibronectin, 86088-83-7
dc.subject.otherChemCAS gamma interferon, 82115-62-6
dc.subject.otherChemCAS insulin receptor substrate 1, 175335-32-7
dc.subject.otherChemCAS nitric oxide, 10102-43-9
dc.subject.otherChemCAS protein kinase B, 148640-14-6
dc.subject.otherChemCAS reduced nicotinamide adenine dinucleotide phosphate oxidase, 9032-22-8
dc.subject.otherChemCAS toll like receptor 2, 203811-81-8
dc.subject.otherChemCAS toll like receptor 4, 203811-83-0
dc.subject.otherChemCAS vasculotropin A, 489395-96-2
dc.subject.otherChemCAS vasculotropin C, 171342-42-0, 185969-81-7
dc.subject.otherChemCAS vasculotropin D, 193363-12-1
dc.subject.otherChemCAS Antigens, CD
dc.subject.otherChemCAS CD66 antigens
dc.subject.otherChemCAS Carcinoembryonic Antigen
dc.subject.otherChemCAS Ceacam1 protein, mouse
dc.subject.otherChemCAS Cell Adhesion Molecules
dc.subject.otherChemCAS Nitric Oxide, 10102-43-9
dc.subject.otherChemCAS Nitric Oxide Synthase Type III, 1.14.13.39
dc.subject.otherChemCAS Nos3 protein, mouse, 1.14.13.39
dc.subject.otherChemCAS Vascular Cell Adhesion Molecule-1
dc.subject.otherIndex beta catenin
dc.subject.otherIndex carcinoembryonic antigen related cell adhesion molecule 1
dc.subject.otherIndex CD3 antigen
dc.subject.otherIndex CD8 antigen
dc.subject.otherIndex endothelial nitric oxide synthase
dc.subject.otherIndex fibronectin
dc.subject.otherIndex gamma interferon
dc.subject.otherIndex high density lipoprotein cholesterol
dc.subject.otherIndex insulin receptor substrate 1
dc.subject.otherIndex interleukin 6
dc.subject.otherIndex lipoprotein
dc.subject.otherIndex low density lipoprotein cholesterol
dc.subject.otherIndex messenger RNA
dc.subject.otherIndex monocyte chemotactic protein 1
dc.subject.otherIndex nitric oxide
dc.subject.otherIndex protein kinase B
dc.subject.otherIndex reduced nicotinamide adenine dinucleotide phosphate oxidase
dc.subject.otherIndex toll like receptor 2
dc.subject.otherIndex toll like receptor 4
dc.subject.otherIndex transcription factor FKHR
dc.subject.otherIndex vascular cell adhesion molecule 1
dc.subject.otherIndex vascular endothelial cadherin
dc.subject.otherIndex vasculotropin A
dc.subject.otherIndex vasculotropin C
dc.subject.otherIndex vasculotropin D
dc.subject.otherIndex vasculotropin receptor 1
dc.subject.otherIndex vasculotropin receptor 2
dc.subject.otherIndex animal cell
dc.subject.otherIndex animal experiment
dc.subject.otherIndex animal model
dc.subject.otherIndex animal tissue
dc.subject.otherIndex aorta arch
dc.subject.otherIndex aorta wall
dc.subject.otherIndex article
dc.subject.otherIndex atherosclerosis
dc.subject.otherIndex blood vessel permeability
dc.subject.otherIndex controlled study
dc.subject.otherIndex endothelium cell
dc.subject.otherIndex enzyme activity
dc.subject.otherIndex fatty acid blood level
dc.subject.otherIndex fatty liver
dc.subject.otherIndex histopathology
dc.subject.otherIndex hypercholesterolemia
dc.subject.otherIndex in vitro study
dc.subject.otherIndex insulin clearance
dc.subject.otherIndex leukocyte
dc.subject.otherIndex leukocyte adherence
dc.subject.otherIndex lipid composition
dc.subject.otherIndex lipid peroxidation
dc.subject.otherIndex lipid storage
dc.subject.otherIndex macrophage
dc.subject.otherIndex male
dc.subject.otherIndex mouse
dc.subject.otherIndex nonhuman
dc.subject.otherIndex oxidative stress
dc.subject.otherIndex priority journal
dc.subject.otherIndex protein binding
dc.subject.otherIndex protein phosphorylation
dc.subject.otherIndex vascular lesion
dc.subject.otherIndex vasodilatation
dc.subject.otherIndex fatty liver disease
dc.subject.otherIndex metabolic syndrome
dc.subject.otherIndex NEFA
dc.subject.otherIndex obesity
dc.subject.otherIndex Animals
dc.subject.otherIndex Antigens, CD
dc.subject.otherIndex Aorta, Thoracic
dc.subject.otherIndex Carcinoembryonic Antigen
dc.subject.otherIndex Cattle
dc.subject.otherIndex Cell Adhesion
dc.subject.otherIndex Cell Adhesion Molecules
dc.subject.otherIndex Cells, Cultured
dc.subject.otherIndex Endothelium, Vascular
dc.subject.otherIndex Leukocytes
dc.subject.otherIndex Lipid Peroxidation
dc.subject.otherIndex Macrophages
dc.subject.otherIndex Male
dc.subject.otherIndex Mice
dc.subject.otherIndex Mice, Inbred C57BL
dc.subject.otherIndex Mice, Knockout
dc.subject.otherIndex Nitric Oxide
dc.subject.otherIndex Nitric Oxide Synthase Type III
dc.subject.otherIndex Oxidative Stress
dc.subject.otherIndex Plaque, Atherosclerotic
dc.subject.otherIndex RNA Interference
dc.subject.otherIndex Signal Transduction
dc.subject.otherIndex Vascular Cell Adhesion Molecule-1
dc.subject.otherKeywordPlus CELL-ADHESION MOLECULE-1
dc.subject.otherKeywordPlus NITRIC-OXIDE SYNTHASE
dc.subject.otherKeywordPlus NECROSIS-FACTOR-ALPHA
dc.subject.otherKeywordPlus ENDOTHELIAL-CELLS
dc.subject.otherKeywordPlus NONALCOHOLIC STEATOHEPATITIS
dc.subject.otherKeywordPlus INSULIN-RESISTANCE
dc.subject.otherKeywordPlus OXIDATIVE STRESS
dc.subject.otherKeywordPlus BETA-CATENIN
dc.subject.otherKeywordPlus EXPRESSION
dc.subject.otherKeywordPlus MICE
dc.subject.otherWOS Endocrinology and Metabolism
dc.subject.otherWOS Physiology


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