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Updated: Feb 1, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
CX3CL1-Fc treatment prevents atherosclerosis in Ldlr KO mice
Matthew Riopel1, Melanie Vassallo2, Erik Ehinger2
1Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Insights
A novel CX3CL1-Fc treatment significantly reduced atherosclerosis in mice by inhibiting monocyte adhesion to endothelial cells. This approach offers a potential therapeutic strategy for cardiovascular disease by targeting key inflammatory interactions.
Area of Science:
- Cardiovascular Research
- Immunology
- Atherosclerosis Pathogenesis
Background:
- Atherosclerosis, a primary cause of cardiovascular disease, involves monocyte-endothelial cell interactions mediated by CX3CR1 and fractalkine (CX3CL1).
- Targeting this ligand-receptor pair presents a potential therapeutic avenue to mitigate atherosclerotic plaque development.
Purpose of the Study:
- To investigate the efficacy of a long-acting CX3CL1 agonist (CX3CL1-Fc) in reducing atherosclerosis.
- To determine if preventing monocyte-endothelial cell interactions can inhibit atherosclerotic progression.
Main Methods:
- A long-acting soluble form of CX3CL1 (CX3CL1-Fc) was generated by fusing the chemokine domain of CX3CL1 to the mouse Fc region.
- CX3CL1-Fc was administered to Ldlr knockout mice on an atherogenic diet for 4 months, with subsequent analysis of atherosclerotic lesions and immune cell populations.
Main Results:
- CX3CL1-Fc treatment led to reduced aortic lesion size and necrotic core area in mice.
- Flow cytometry revealed decreased M1-like macrophages and T cells in treated mice.
- In vitro and in vivo models demonstrated reduced monocyte/leukocyte adhesion and rolling following CX3CL1-Fc administration.
Conclusions:
- CX3CL1-Fc effectively inhibits monocyte-endothelial cell adhesion.
- This therapeutic strategy shows promise in reducing diet-induced atherosclerosis and warrants further investigation for cardiovascular disease treatment.
Objective:
Atherosclerosis is a major cause of cardiovascular disease. Monocyte-endothelial cell interactions are partly mediated by expression of monocyte CX3CR1 and endothelial cell fractalkine (CX3CL1). Interrupting the interaction between this ligand-receptor pair should reduce monocyte binding to the endothelial wall and reduce atherosclerosis. We sought to reduce atherosclerosis by preventing monocyte-endothelial cell interactions through use of a long-acting CX3CR1 agonist.
Methods:
In this study, the chemokine domain of CX3CL1 was fused to the mouse Fc region to generate a long-acting soluble form of CX3CL1 suitable for chronic studies. CX3CL1-Fc or saline was injected twice a week (30 mg/kg) for 4 months into Ldlr knockout (KO) mice on an atherogenic western diet.
Results:
CX3CL1-Fc-treated Ldlr KO mice showed decreased en face aortic lesion surface area and reduced aortic root lesion size with decreased necrotic core area. Flow cytometry analyses of CX3CL1-Fc-treated aortic wall cell digests revealed a decrease in M1-like polarized macrophages and T cells. Moreover, CX3CL1-Fc administration reduced diet-induced atherosclerosis after switching from an atherogenic to a normal chow diet. In vitro monocyte adhesion studies revealed that CX3CL1-Fc treatment caused fewer monocytes to adhere to a human umbilical vein endothelial cell monolayer. Furthermore, a dorsal window chamber model demonstrated that CX3CL1-Fc treatment decreased in vivo leukocyte adhesion and rolling in live capillaries after short-term ischemia-reperfusion.
Conclusion:
These results indicate that CX3CL1-Fc can inhibit monocyte/endothelial cell adhesion as well as reduce atherosclerosis.
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