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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Ceacam1 deletion causes vascular alterations in large vessels
American Journal of Physiology - Endocrinology and Metabolism, Volume 305, No. 4, Year 2013
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Description
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.
Authors & Co-Authors
Najjar, Sonia M.
United States, Toledo
College of Medicine and Life Sciences
Ledford, Kelly J.
United States, Toledo
College of Medicine and Life Sciences
Abdallah, Simon L.
United States, Toledo
College of Medicine and Life Sciences
Paus, Alexander
Germany, Duisburg
Universität Duisburg-essen
Russo, Lucia
United States, Toledo
College of Medicine and Life Sciences
Kaw, Meenakshi K.
United States, Toledo
College of Medicine and Life Sciences
Ramakrishnan, Sadeesh K.
United States, Toledo
College of Medicine and Life Sciences
Muturi, Harrison T.
United States, Toledo
College of Medicine and Life Sciences
Raphael, Christian K.
United States, Toledo
College of Medicine and Life Sciences
Lester, Sumona Ghosh
United States, Toledo
College of Medicine and Life Sciences
Heinrich, Garrett
United States, Toledo
College of Medicine and Life Sciences
Pierre, Sandrine V.
United States, Toledo
College of Medicine and Life Sciences
Benndorf, R. A.
Germany, Wurzburg
Julius-maximilians-universität Würzburg
Kleff, Veronika
Germany, Duisburg
Universität Duisburg-essen
Jaffa, Ayad A.
Lebanon, Beirut
American University of Beirut
Levy, Emile
Canada, Montreal
Université de Montréal, Faculté de Médecine
Vazquez, Guillermo
United States, Toledo
College of Medicine and Life Sciences
Goldberg, Ira J.
United States, New York
Columbia University
Beauchemin, Nicole
Canada, Montreal
Rosalind and Morris Goodman Cancer Research Centre
Scalia, Rosario
United States, Philadelphia
Temple University
Ergün, Süleyman
Germany, Duisburg
Universität Duisburg-essen
Germany, Wurzburg
Julius-maximilians-universität Würzburg
Statistics
Citations: 32
Authors: 21
Affiliations: 8
Identifiers
Doi:
10.1152/ajpendo.00266.2013
ISSN:
01931849
e-ISSN:
15221555