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KMID : 0368120080380050244
Korean Circulation Journal
2008 Volume.38 No. 5 p.244 ~ p.249
Macrophage Depletion by Clodronate Liposomes Suppresses Neointimal Formation After Carotid Artery Injury in Apolipoprotein E-Deficient Mice
Hong Soon-Jun

Ahn Tae-Hoon
Shim Wan-Ju
Park Seong-Mi
Choi Jong-Il
Park Jae-Seuk
Lim Sang-Yup
Lim Do-Sun
Park Chang-Gyu
Seo Hong-Seog
Abstract
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].

Subjects 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¡¾7.4% at baseline, 6.8¡¾4.9% at 24 hours and 0.7¡¾0.3% 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¡¾6.5 vs. 68.7¡¾7.6%, respectively, p<0.05) and at week 4 (37.3¡¾8.5 vs. 62.6¡¾9.4%, respectively, p<0.05). The interleukin (IL)-6 and tumor necrosis factor (TNF)-¥á concentrations were significantly decreased in the clodronate group at week 4 (12.3¡¾2.5 vs. 22.9¡¾3.5 pg/mL, respectively, p<0.05 for IL-6 and 16.6¡¾2.2 vs. 43.6¡¾6.1 pg/mL, respectively, p<0.05 for TNF-¥á). The plaque volume was significantly greater in the control group at week 2 (0.345¡¾0.063 vs. 0.153¡¾0.053 mm2, respectively, p<0.05) and at week 4 (0.320¡¾0.027 vs. 0.167¡¾0.070 mm2, 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.
KEYWORD
Clodronate, Macrophages, Inflammation
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