Macrophage depletion by clodronate liposomes suppresses neointimal formation after carotid artery injury in apolipoprotein E-deficient mice

Background and Objectives: Clodronate liposomes deplete phagocytic cells, thereby suppressing inflammation after vascular injury. We compared the effect of clodronate liposomes on macrophage depletion and neointimal formation in apolipoprotein E-deficient mice [ApoE (-) mice]. Materials and Methods: ApoE (-) mice were randomly assigned to the clodronate liposomes group (Clodronate Group, n = 7) and the vehicle liposomes group (Control Group, n=7). Clodronate (0.1 mL/10 g) was injected via the tail vein starting 2 days (d-2) before left common carotid artery injury. Results: The percentage of blood monocytes was subsequently decreased after clodronate injection (14.0 ± 7.4% at baseline, 6.8 ± 4.9% at 24 hours and 0.7 ± 0.3% at 1 week after the clodronate liposome injection). The percentage of macrophages in the plaque area was significantly lower in the clodronate group at week 2 (32.0 ± 6.5 vs. 68.7 ± 7.6%, respectively, p < 0.05) and at week 4 (37.3 ± 8.5 vs. 62.6 ± 9.4%, respectively, p < 0.05). The interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations were significantly decreased in the clodronate group at week 4 (12.3 ± 2.5 vs. 22.9 ± 3.5 pg/mL, respectively, p < 0.05 for IL-6 and 16.6 ± 2.2 vs. 43.6 ± 6.1 pg/mL, respectively, p < 0.05 for TNF-α). The plaque volume was significantly greater in the control group at week 2 (0.345 ± 0.063 vs. 0.153 ± 0.053 mm², respectively, p < 0.05) and at week 4 (0.320 ± 0.027 vs. 0.167 ± 0.070 mm ², respectively, p < 0.05). Conclusion: Intravenous administration of clodronate liposomes depleted monocytes and macrophages, and so this reduced the inflammatory markers and neointimal formation in ApoE (-) mice.