Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis
Philippe Lesnik, … , Christopher A. Haskell, Israel F. Charo
Philippe Lesnik, … , Christopher A. Haskell, Israel F. Charo
Published February 1, 2003
Citation Information: J Clin Invest. 2003;111(3):333-340. https://doi.org/10.1172/JCI15555.
View: Text | PDF
Article Vascular biology

Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis

  • Text
  • PDF
Abstract

The hallmark of early atherosclerosis is the accumulation of lipid-laden macrophages in the subendothelial space. Circulating monocytes are the precursors of these “foam cells,” and recent evidence suggests that chemokines play important roles in directing monocyte migration from the blood to the vessel wall. Fractalkine (FK) is a structurally unusual chemokine that can act either as a soluble chemotactic factor or as a transmembrane-anchored adhesion receptor for circulating leukocytes. A polymorphism in the FK receptor, CX3CR1, has been linked to a decrease in the incidence of coronary artery disease. To determine whether FK is critically involved in atherogenesis, we deleted the gene for CX3CR1 and crossed these mice into the apoE–/– background. Here we report that FK is robustly expressed in lesional smooth muscle cells, but not macrophages, in apoE–/– mice on a high-fat diet. CX3CR1–/– mice have a significant reduction in macrophage recruitment to the vessel wall and decreased atherosclerotic lesion formation. Taken together, these data provide strong evidence that FK plays a key role in atherogenesis.

Authors

Philippe Lesnik, Christopher A. Haskell, Israel F. Charo

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Immunolocalization of FK in atherosclerotic lesions. Mice lacking apoE (...
Immunolocalization of FK in atherosclerotic lesions. Mice lacking apoE (apoE–/– mice) were maintained on the Western diet for 10 weeks. Serial sections were cut at the level of the aortic valve leaflets and incubated with antibodies. (a) Staining of FK (visualized as red). (b) Staining of macrophages (visualized as green). (c) Merged image of a and b. (d) Nuclei were stained with DAPI (blue) and the image was captured with a multiband (DAPI/phycoerythrin/FITC) filter. Original magnification: ×200.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts