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Updated: Jul 9, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
CXCR3 antagonist NBI-74330 attenuates atherosclerotic plaque formation in LDL receptor-deficient mice
Eva J A van Wanrooij1, Saskia C A de Jager, Thomas van Es
1Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Objective:
The chemokine receptor CXCR3 is implicated in migration of leukocytes to sites of inflammation. Antagonizing CXCR3 may be a strategy to inhibit inflammation-induced leukocyte migration and subsequently reduce atherosclerosis. We used the CXCR3 specific antagonist NBI-74330 to block CXCR3-mediated signaling in peritonitis and diet-induced atherosclerosis.
Methods And Results:
Antagonizing CXCR3 with NBI-74330 resulted in a significant reduction in CD4+ T cell and macrophage migration to the peritoneal cavity, which was as shown in ex vivo migration studies totally CXCR3 dependent. Atherosclerotic lesion formation in the aortic valve leaflet area and the entire aorta was significantly inhibited in NBI-74330 treated mice. Lymph nodes draining from the aortic arch were significantly smaller in treated mice and were enriched in regulatory T cells and contained fewer activated T cells, whereas the markers for regulatory T cells within the lesion were enhanced after NBI-74330 treatment.
Conclusions:
This study shows for the first time that treatment with a CXCR3 antagonist results in attenuating atherosclerotic lesion formation by blocking direct migration of CXCR3+ effector cells from the circulation into the atherosclerotic plaque and by beneficially modulating the inflammatory response in the lesion and the lymph nodes draining from the atherosclerotic lesion.
Insights
Blocking the chemokine receptor CXCR3 with NBI-74330 significantly reduced leukocyte migration and attenuated atherosclerosis development. This CXCR3 antagonism offers a potential therapeutic strategy for inflammatory diseases like atherosclerosis.
Area of Science:
- Immunology
- Cardiovascular Research
Background:
- The chemokine receptor CXCR3 (CXCR3) plays a role in leukocyte trafficking to inflammatory sites.
- Inhibition of CXCR3-mediated migration may reduce inflammation and atherosclerosis.
Purpose of the Study:
- To investigate the therapeutic potential of antagonizing CXCR3 using NBI-74330 in models of peritonitis and atherosclerosis.
Main Methods:
- Utilized NBI-74330, a specific CXCR3 antagonist, in mouse models.
- Assessed leukocyte migration, atherosclerotic lesion formation, and immune cell populations in lymph nodes and lesions.
Main Results:
- NBI-74330 treatment significantly reduced CD4+ T cell and macrophage migration, dependent on CXCR3.
- Atherosclerotic lesion formation in the aorta and aortic valve was significantly inhibited.
- Treated mice showed smaller lymph nodes with increased regulatory T cells and decreased activated T cells.
Conclusions:
- CXCR3 antagonism attenuates atherosclerotic lesion formation by inhibiting effector cell migration.
- This approach beneficially modulates the inflammatory response within lesions and draining lymph nodes.
