Macrophage Depletion by Clodronate Liposomes Suppresses Neointimal Formation After Carotid Artery Injury in Apolipoprotein E-Deficient Mice.
10.4070/kcj.2008.38.5.244
- Author:
Soon Jun HONG
1
;
Tae Hoon AHN
;
Wan Joo SHIM
;
Seong Mi PARK
;
Jong Il CHOI
;
Jae Suk PARK
;
Sang Yup LIM
;
Do Sun LIM
;
Chang Gyu PARK
;
Hong Seog SEO
Author Information
1. Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea. psyche94@hanmail.net
- Publication Type:Original Article
- Keywords:
Clodronate;
Macrophages;
Inflammation
- MeSH:
Administration, Intravenous;
Animals;
Apolipoproteins;
Apolipoproteins E;
Carotid Arteries;
Carotid Artery Injuries;
Carotid Artery, Common;
Clodronic Acid;
Inflammation;
Interleukin-6;
Interleukins;
Liposomes;
Macrophages;
Mice;
Monocytes;
Phagocytes;
Tumor Necrosis Factor-alpha;
Vascular System Injuries;
Veins
- From:Korean Circulation Journal
2008;38(5):244-249
- CountryRepublic of Korea
- Language:English
-
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]. 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)-alpha 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-alpha). 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 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.