title: Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes.
abstract: Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse.
  
  
  
  Apo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced.
  
  
  
  Ang-1 specifically increases circulating Gr1+inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.
authors.affiliation: Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, U.K.|Gustav Born Centre for Vascular Biology and BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujisawa
authors.affiliation: Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, U.K; asif.ahmed@aston.ac.uk k.wang@aston.ac.uk.|Gustav Born Centre for Vascular Biology and BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Cardiology, Duke University Medical Centre, Durham, NC 27710, USA.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Niu
authors.affiliation: Multidisciplinary Cardiovascular Research Centre, School of Biological Sciences, University of Leeds, Leeds, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Egginton
authors.affiliation: Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, U.K.|Gustav Born Centre for Vascular Biology and BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hewett
authors.affiliation: Department of Medicine, Division of Cardiology, Duke University Medical Centre, Durham, NC 27710, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kontos
authors.affiliation: Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, U.K; asif.ahmed@aston.ac.uk k.wang@aston.ac.uk.|Gustav Born Centre for Vascular Biology and BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Asif
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D000950:Antigens, Ly; D001057:Apolipoproteins E; D039481:CD11b Antigen; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C480309:Ly6G antigen, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
keywords: Angiopoietin-1 ; Atherosclerosis ; Monocytes