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Updated: Jun 19, 2026
Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
CCR2 receptor blockade alters blood monocyte subpopulations but does not affect atherosclerotic lesions in apoE(-/-)
Robert J Aiello1, Bret D Perry, Patricia-Ann Bourassa
1Pfizer Global Research and Development, Department of Cardiovascular and Metabolic Diseases, Eastern Point Road, Groton, CT 06340, United States. robert.j.aiello@pfizer.com
Objective:
The CCR2 receptor plays a crucial role in monocyte recruitment and has been implicated as a contributing factor to atherosclerosis. CCR2 receptor deletion leads to significant inhibition of lesion development. Our objective was to determine if CCR2 receptor blockade with a small molecule would have a beneficial effect of decreasing established lesions.
Methods And Results:
We demonstrated that CCR2 blockade had no significant effect on advanced lesions or the progression of fatty streaks. CCR2 blockade in mice resulted in elevations in plasma CCL2 levels and a significant reduction in the plasma Ly-6C(hi) subpopulations of monocytes expressing the CCR2 receptor. Neither CCL2 elevation nor margination of the Ly-6C(hi) population was observed in CCR2(-/-) mice.
Conclusions:
CCR2 receptor blockade with a small molecule antagonist at dose levels showing efficacy in several inflammatory models did not show a beneficial effect in murine models of atherosclerosis. Elevations in CCL2 and margination of Ly-6C(hi) cells demonstrate that the role of CCR2 in controlling monocyte levels goes beyond the control of monocyte emigration.
Insights
CCR2 receptor blockade did not reduce atherosclerosis in mice, despite its role in monocyte recruitment. Blocking CCR2 increased CCL2 levels and altered monocyte populations, suggesting complex roles beyond simple emigration.
Area of Science:
- Immunology
- Cardiovascular Research
- Pharmacology
Background:
- The CCR2 receptor is vital for monocyte recruitment and implicated in atherosclerosis development.
- CCR2 receptor deletion significantly inhibits lesion progression.
- Investigating therapeutic blockade of CCR2 is a potential strategy for atherosclerosis.
Purpose of the Study:
- To evaluate the efficacy of small molecule CCR2 receptor blockade in reducing established atherosclerotic lesions.
- To determine if inhibiting CCR2 function impacts atherosclerosis progression in murine models.
Main Methods:
- Administration of a small molecule CCR2 receptor antagonist in mouse models of atherosclerosis.
- Assessment of lesion development and progression.
- Analysis of plasma CCL2 levels and monocyte subpopulations (Ly-6C(hi)).
Main Results:
- CCR2 blockade showed no significant effect on established atherosclerotic lesions or fatty streak progression.
- Blockade led to elevated plasma CCL2 and reduced Ly-6C(hi) monocytes expressing CCR2.
- These effects (CCL2 elevation, Ly-6C(hi) margination) were not observed in CCR2(-/-) mice.
Conclusions:
- Small molecule CCR2 receptor antagonist did not demonstrate a beneficial effect in murine atherosclerosis models.
- Elevated CCL2 and margination of Ly-6C(hi) cells suggest CCR2's role in monocyte regulation extends beyond emigration.
- Further research is needed to understand the complex role of CCR2 in atherosclerosis.
