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 ...
    • 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)
    • Vascular Malformations (Apr 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
Alternative macrophages in atherosclerosis: not always protective!
Benoit Pourcet, Bart Staels
Benoit Pourcet, Bart Staels
Published February 19, 2018
Citation Information: J Clin Invest. 2018;128(3):910-912. https://doi.org/10.1172/JCI120123.
View: Text | PDF
Commentary

Alternative macrophages in atherosclerosis: not always protective!

  • Text
  • PDF
Abstract

Atherosclerosis is a chronic inflammatory disease of the vasculature that is initiated by cholesterol deposition into the arterial wall, which triggers the infiltration of immune and inflammatory cells, including monocytes and macrophages. As atherosclerotic plaques progress, localized hypoxia promotes compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage. Macrophages with different phenotypes, ranging from classical inflammatory subtypes to alternatively activated antiinflammatory macrophages, have been identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging CD163+ macrophages are present in neovessel- and hemorrhage-rich areas; however, the role of these macrophages in atherogenesis has been unclear. In this issue of the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction. This study thus identifies proatherogenic properties of CD163+ macrophages, which previously were thought to be beneficial.

Authors

Benoit Pourcet, Bart Staels

×

Figure 1

Alternative CD163+ macrophages associate with atherosclerotic plaque hemorrhage and leakage.

Options: View larger image (or click on image) Download as PowerPoint
Alternative CD163+ macrophages associate with atherosclerotic plaque hem...
CD163+ M(Hb) macrophages are abundant in hemorrhage areas, in which erythrolysis provides high amounts of Hb (i). In complex with Hp, Hb is scavenged by CD163 and induces the expression of FPN, which promotes intracellular Fe2+ depletion (i). Ferrous iron efflux leads to decreased prolyl hydroxylase 2 (PHD2) activity and subsequent stabilization of HIF1α, which enhances VEGF expression (i) and intraplaque neovascularization. VEGF promotes VEGFR2-dependent VE-cadherin internalization (ii) and neovessel leakage (ii). VEGF also enhances VCAM expression and macrophage infiltration (iii), therby increasing plaque progression and erosion. ECs, endothelial cells; SMCs, smooth muscle cells.

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

Sign up for email alerts