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Updated: Jan 20, 2026
Porcine Model of Infrarenal Abdominal Aortic Aneurysm
Published on: November 21, 2019
Involvement of macrophage-derived exosomes in abdominal aortic aneurysms development
Yidong Wang1, Liangliang Jia1, Yao Xie1
1Department of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Key Lab of Cardiovascular Disease of Zhejiang Province, Hangzhou, Zhejiang, PR China.
Background And Aims:
Abdominal aortic aneurysm (AAA) is characterized by infiltration of inflammatory cells, extracellular matrix (ECM) degradation, and dysfunction of vascular smooth muscle cells (VSMCs). Recent studies reported that exosomes mediate intercellular communication and are involved in different diseases. Whether exosomes play a role in AAA is poorly understood. Hence, this study evaluated the function of exosomes in AAA development.
Methods:
The presence of exosomes in human and calcium phosphate (CaPO4)-induced AAA tissues was determined by immunofluorescence staining of CD63 and Alix. GW4869, an inhibitor of exosome biogenesis, was intraperitoneally injected into CaPO4-induced AAA tissues to evaluate the effects of exosomal inhibition on AAA development. To explore the underlying mechanisms, the human monocytic cell line THP-1 was differentiated into macrophages, and exosomes were collected from macrophages. VSMCs were treated with macrophage-derived exosomes, and the expression of matrix metalloproteinase-2 (MMP-2) was evaluated. The activation of mitogen-activated protein kinases (MAPKs) pathways was also investigated in vitro and in vivo.
Results:
Exosomes were detected in the adventitia of aneurysmal tissues obtained from humans and mice. They were mainly expressed in clusters of macrophages. Intraperitoneal injection of GW4869 for two weeks significantly attenuated the progression of CaPO4-induced AAA, preserved elastin integrity and decreased MMP-2 expression. Similarly, administration of GW4869 suppressed the systemic and aneurysmal exosome generation. In vitro, treatment with macrophage-derived exosomes elevated MMP-2 expression in human VSMCs, while pre-treatment with GW4869 abolished these effects. It was also found that JNK and p38 pathways mediated the production of MMP-2 in VSMCs following treatment with macrophage-derived exosomes.
Conclusions:
This study suggests that exosomes derived from macrophages are involved in the pathogenesis of AAA. Macrophage-derived exosomes trigger MMP-2 expression in VSMC via JNK and p38 pathways. GW4869 supplementation attenuates CaPO4-induced AAA in mice.
Insights
Macrophage-derived exosomes contribute to abdominal aortic aneurysm (AAA) development by increasing matrix metalloproteinase-2 (MMP-2) in vascular cells. Inhibiting exosome production with GW4869 attenuated AAA progression in a mouse model.
Area of Science:
- Cell Biology
- Vascular Biology
- Biochemistry
Background:
- Abdominal aortic aneurysm (AAA) involves inflammation, extracellular matrix degradation, and vascular smooth muscle cell (VSMC) dysfunction.
- Exosomes mediate intercellular communication and are implicated in various diseases, but their role in AAA remains unclear.
Purpose of the Study:
- To investigate the function of exosomes in the development of abdominal aortic aneurysm (AAA).
- To elucidate the mechanisms by which exosomes contribute to AAA pathogenesis.
Main Methods:
- Exosomes in human and mouse AAA tissues were identified using immunofluorescence (CD63, Alix).
- The effect of exosome biogenesis inhibitor GW4869 on calcium phosphate (CaPO4)-induced AAA in mice was evaluated.
- Macrophage-derived exosomes were isolated and applied to VSMCs to assess their impact on matrix metalloproteinase-2 (MMP-2) expression and mitogen-activated protein kinase (MAPK) pathway activation.
Main Results:
- Exosomes were detected in AAA tissues, primarily within macrophages.
- GW4869 treatment significantly reduced AAA progression, preserved elastin, and decreased MMP-2 expression in mice.
- Macrophage-derived exosomes increased MMP-2 expression in VSMCs via JNK and p38 MAPK pathways, effects abolished by GW4869 pre-treatment.
Conclusions:
- Exosomes derived from macrophages play a significant role in AAA pathogenesis.
- Macrophage-derived exosomes promote VSMC MMP-2 expression through JNK and p38 signaling.
- Inhibition of exosome generation with GW4869 offers a potential therapeutic strategy for AAA.
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