Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • 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
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice
Brian C. Tieu, … , Ronald G. Tilton, Allan R. Brasier
Brian C. Tieu, … , Ronald G. Tilton, Allan R. Brasier
Published November 16, 2009
Citation Information: J Clin Invest. 2009;119(12):3637-3651. https://doi.org/10.1172/JCI38308.
View: Text | PDF
Research Article Article has an altmetric score of 6

An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice

  • Text
  • PDF
Abstract

Vascular inflammation contributes to cardiovascular diseases such as aortic aneurysm and dissection. However, the precise inflammatory pathways involved have not been clearly defined. We have shown here that subcutaneous infusion of Ang II, a vasopressor known to promote vascular inflammation, into older C57BL/6J mice induced aortic production of the proinflammatory cytokine IL-6 and the monocyte chemoattractant MCP-1. Production of these factors occurred predominantly in the tunica adventitia, along with macrophage recruitment, adventitial expansion, and development of thoracic and suprarenal aortic dissections. In contrast, a reduced incidence of dissections was observed after Ang II infusion into mice lacking either IL-6 or the MCP-1 receptor CCR2. Further analysis revealed that Ang II induced CCR2+CD14hiCD11bhiF4/80– macrophage accumulation selectively in aortic dissections and not in aortas from Il6–/– mice. Adoptive transfer of Ccr2+/+ monocytes into Ccr2–/– mice resulted in selective monocyte uptake into the ascending and suprarenal aorta in regions of enhanced ROS stress, with restoration of IL-6 secretion and increased incidence of dissection. In vitro, coculture of monocytes and aortic adventitial fibroblasts produced MCP-1– and IL-6–enriched conditioned medium that promoted differentiation of monocytes into macrophages, induced CD14 and CD11b upregulation, and induced MCP-1 and MMP-9 expression. These results suggest that leukocyte-fibroblast interactions in the aortic adventitia potentiate IL-6 production, inducing local monocyte recruitment and activation, thereby promoting MCP-1 secretion, vascular inflammation, ECM remodeling, and aortic destabilization.

Authors

Brian C. Tieu, Chang Lee, Hong Sun, Wanda LeJeune, Adrian Recinos 3rd, Xiaoxi Ju, Heidi Spratt, Dong-Chuan Guo, Dianna Milewicz, Ronald G. Tilton, Allan R. Brasier

×

Figure 1

Ang II infusion in older WT mice induces aortic cytokines and dissecting aortic aneurysms.

Options: View larger image (or click on image) Download as PowerPoint
Ang II infusion in older WT mice induces aortic cytokines and dissecting...
(A) Development of suprarenal abdominal and thoracic aortic dissections; dissected aortae were photographed oriented with the kidney to the left and heart to the right. (B) Photographs of sham- and Ang II–treated groups (top) and Movat staining of their cross sections (bottom). Original magnification, ×40. See Supplemental Figure 5 for enlarged photograph. (C) Secreted IL-6 and MCP-1 concentrations in aortic explant culture from sham- (n = 8) or Ang II–infused mice after 10 days (n = 12) for mice younger than 2 months of age or 7–10 months of age. Top panels show measurements after incubation of the entire aorta; bottom panels show cytokine concentrations in explant media normalized to aortic dry weight. Data are mean ± SEM. Groups were compared by 2-way ANOVA, using treatment (Ang II) or age as independent variables. For each comparison, the P value is displayed for age effect, Ang II effect, and the interaction effect of Ang II with age (AngII*age). (D) Immunofluorescence staining for macrophages (MOMA-2), AoAFs (ERTR7), IL-6, and MCP-1 in transverse cryosections (6 μm) of ascending aorta from sham- and Ang II–treated mice for 6 days. Nuclei were stained with DAPI (blue). Elastic lamellae of the media are green (autofluorescence). Positive staining is red (Alexa Fluor 568–conjugated secondary Ab). Original magnification, ×200.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 4 patents
182 readers on Mendeley
1 readers on CiteULike
See more details