CD146 extracellular vesicles accumulate at atherosclerotic lesions, reducing inflammation and atheroma burden

Cléa Dubrou1, Muriel G Blin2, Karim Fallague2

  • 1Aix-Marseille Univ, INSERM, INRAE, C2VN, Marseille, France; Assistance Publique-Hôpitaux de Marseille, APHM, Biogenopole, CHU La Timone, Marseille, France.

Atherosclerosis
|June 7, 2026
PubMed

Insights

CD146 extracellular vesicles reduce atherosclerosis by promoting anti-inflammatory macrophage phenotypes. This novel therapeutic approach targets atherosclerotic plaque, offering a potential new treatment for cardiovascular disease.

Area of Science:

  • Cardiovascular Research
  • Cell Biology
  • Immunology

Background:

  • Atherosclerosis is a leading global cause of mortality, necessitating novel therapeutic strategies.
  • CD146, an endothelial cell adhesion molecule, influences macrophage behavior within atherosclerotic plaques.
  • Extracellular vesicles (EVs) show promise as targeted drug delivery systems.

Purpose of the Study:

  • To investigate the atheroprotective potential of CD146-expressing extracellular vesicles (CD146 EVs).
  • To determine the mechanism by which CD146 EVs modulate macrophage phenotype and inflammation.

Main Methods:

  • Generation and purification of CD146 EVs from endothelial cells.
  • In vitro assessment of CD146 EV effects on macrophage polarization via the STAT3/IL-10 pathway.
  • Intravenous administration of labeled CD146 EVs in ApoE-/- mouse model of atherosclerosis, followed by plaque analysis.

Main Results:

  • CD146 EVs induced macrophage polarization towards an anti-inflammatory phenotype in vitro.
  • Labeled CD146 EVs were successfully trafficked and incorporated into atherosclerotic plaques in vivo.
  • ApoE-/- mice treated with CD146 EVs showed significant atherosclerotic plaque reduction and anti-inflammatory macrophage profiles.

Conclusions:

  • CD146 EVs possess atheroprotective properties.
  • Treatment with CD146 EVs modulates macrophage phenotype, reducing inflammation in atherosclerosis.
  • CD146 EVs represent a promising novel therapeutic strategy for atherosclerosis.

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