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Published on: April 3, 2026
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.
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.
Abstract:
Atherosclerosis remains the most important cause of death worldwide despite an extensive therapeutic arsenal. We previously showed that CD146, an adhesion molecule expressed by endothelial cells, is harbored by macrophages in atherosclerotic plaque and allows to reduce CCL5 and subsequent inflammation. As extracellular vesicles may serve as potential clinical delivery devices, we hypothesized that CD146 extracellular vesicles injection could be atheroprotective. We generated and purified extracellular vesicles from mouse endothelial cells deleted or not with CD146. In vitro stimulation of macrophages with CD146 extracellular vesicles induced macrophage polarization towards an anti-inflammatory phenotype through the STAT3/IL-10 axis, whereas CD146-negative extracellular vesicles did not have any effect. We next tracked the trafficking of labeled extracellular vesicles after intravenous injection in atherosclerotic ApoE-/- mice and visualized their incorporation into atheroma. After bi-weekly injections of extracellular vesicles for 6 weeks, only ApoE-/- mice treated with CD146 extracellular vesicles exhibited a significant reduction in atherosclerotic plaque, associated with an anti-inflammatory macrophage phenotype. We thus propose that treatment with CD146 extracellular vesicles could constitute a novel therapeutic option for reducing atherosclerosis.
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