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Updated: Apr 15, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Atypical chemokine receptor 1 deficiency reduces atherogenesis in ApoE-knockout mice
Wuzhou Wan1, Qian Liu1, Michail S Lionakis2
1Molecular Signaling Section, Laboratory of Molecular Immunology (LMI), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Aims:
Atypical chemokine receptor 1 (Ackr1; previously known as the Duffy antigen receptor for chemokines or Darc) is thought to regulate acute inflammatory responses in part by scavenging inflammatory CC and CXC chemokines; however, evidence for a role in chronic inflammation has been lacking. Here we investigated the role of Ackr1 in chronic inflammation, in particular in the setting of atherogenesis, using the apolipoprotein E-deficient (ApoE(-/-)) mouse model.
Methods And Results:
Ackr1(-/-)ApoE(-/-) and Ackr1(+/+)ApoE(-/-) littermates were obtained by crossing ApoE(-/-) mice and Ackr1(-/-) mice on a C57BL/6J background. Ackr1 (+/+)ApoE(-/-)mice fed a Western diet up-regulated Ackr1 expression in the aorta and had markedly increased atherosclerotic lesion size compared with Ackr1(-/-)ApoE(-/-) mice. This difference was observed in both the whole aorta and the aortic root in both early and late stages of the model. Ackr1 deficiency did not affect serum cholesterol levels or macrophage, collagen or smooth muscle cell content in atherosclerotic plaques, but significantly reduced the expression of Ccl2 and Cxcl1 in the whole aorta of ApoE(-/-) mice. In addition, Ackr1 deficiency resulted in a modest decrease in T cell subset frequency and inflammatory mononuclear phagocyte content in aorta and blood in the model.
Conclusions:
Ackr1 deficiency appears to be protective in the ApoE knockout model of atherogenesis, but it is associated with only modest changes in cytokine and chemokine expression as well as T-cell subset frequency and inflammatory macrophage content.
Insights
Atypical chemokine receptor 1 (Ackr1) deficiency protected against atherosclerosis in ApoE knockout mice. This suggests Ackr1 plays a role in chronic inflammation and atherogenesis, impacting chemokine levels and immune cell infiltration.
Area of Science:
- Immunology
- Cardiovascular Biology
- Molecular Biology
Background:
- Atypical chemokine receptor 1 (Ackr1), also known as the Duffy antigen receptor for chemokines (Darc), is implicated in regulating acute inflammatory responses by scavenging chemokines.
- Evidence for Ackr1's role in chronic inflammation, particularly in atherogenesis, has been limited.
Purpose of the Study:
- To investigate the role of Ackr1 in chronic inflammation within the context of atherogenesis.
- To utilize the apolipoprotein E-deficient (ApoE(-/-)) mouse model to study Ackr1's function in atherosclerosis development.
Main Methods:
- Generated Ackr1(-/-)ApoE(-/-) and Ackr1(+/+)ApoE(-/-) littermate mice on a C57BL/6J background.
- Fed mice a Western diet to induce atherosclerosis and analyzed aortic tissue for lesion size, cellular content, and gene expression.
- Assessed serum cholesterol levels, plaque composition, and immune cell populations in aorta and blood.
Main Results:
- Ackr1(+/+)ApoE(-/-) mice exhibited significantly larger atherosclerotic lesions compared to Ackr1(-/-)ApoE(-/-) mice.
- Ackr1 deficiency reduced Ccl2 and Cxcl1 expression in the aorta and led to a modest decrease in T cell and inflammatory monocyte populations.
- Serum cholesterol and plaque cellular composition (macrophages, collagen, smooth muscle cells) were not significantly affected by Ackr1 deficiency.
Conclusions:
- Ackr1 deficiency demonstrates a protective effect in the ApoE knockout mouse model of atherosclerosis.
- The protective role is associated with reduced chemokine expression and altered immune cell infiltration, though changes are modest.
- These findings highlight a potential role for Ackr1 in the chronic inflammatory processes underlying atherogenesis.
